bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly purified CD34-positive cells reconstitute hematopoiesis.
Authors: Civin C I , Trischmann T , Kadan N S , Davis J , Noga S , Cohen K , Duffy B , Groenewegen I , Wiley J , Law P , Hardwick A , Oldham F , Gee A
Published: February 2017

PURPOSE

The objective of this study was to characterize CD34+ cell grafts, obtained using a novel technique, from children undergoing autologous bone marrow transplantation (BMT) for cancer therapy. In particular, we wanted to determine if the CD34+ marrow cell grafts generated hematopoietic reconstitution, since a positive result would motivate further development and use of this methodology.

PATIENTS AND METHODS

This pilot feasibility clinical trial involved 13 patients < or = 25 years of age with advanced solid tumors, including seven children with neuroblastoma. Harvested bone marrow underwent immunomagnetic CD34+ selection.

RESULTS

In three of 13 enrolled patients, low purities of the CD34+ preparations disqualified the use of the CD34+ marrow grafts. Ten patients received myeloablative chemotherapy with etoposide, carboplatin, and cyclophosphamide, then were transplanted with CD34+ marrow grafts. In the 10 patients transplanted with CD34(+)-selected cells, the CD34+ cell purity (nucleated RBCs excluded) in the cell graft preparation was 91% total cell recovery from the starting light-density cells 2.2%, CD34+ cell recovery 38%, colony-forming unit-granulocyte-macrophage (CFU-GM) recovery 23%, and estimated tumor-cell depletion 2.6 logs (medians). The CD34+ marrow grafts administered to these patients contained a median of 2.3 x 10(6) nucleated cells, 1.4 x 10(6) CD34+ cells, and 1.3 x 10(4) CFU-GM per kilogram patient weight. Most patients experienced only the toxicities previously observed with this myeloblative chemotherapy regimen, although two unusual toxicities were observed. All 10 patients transplanted with CD34+ cell grafts engrafted.

CONCLUSION

The CD34+ purified grafts were enriched in stem/progenitor cells, with five of these 10 preparations containing > or = 94% CD34+ cells. Engraftment with CD34(+)-purified cell grafts as pure as 99% confirms that autologous CD34+ cells, alone, are sufficient to provide hematopoietic rescue for myeloablated patients. The best purification results were obtained on small marrow harvests from patients with neuroblastoma. The engraftment of highly purified CD34+ cells obtained by this technology and the antitumor effect of the transplant, by which two of 10 poor prognosis patients remain clinically free of tumor, have stimulated further clinical trials.
Clinical utility of external immunoscintigraphy with the IMMU-4 technetium-99m Fab' antibody fragment in patients undergoing surgery for carcinoma of the colon and rectum: results of a pivotal, phase III trial. The Immunomedics Study Group.
Authors: Moffat F L , Pinsky C M , Hammershaimb L , Petrelli N J , Patt Y Z , Whaley F S , Goldenberg D M
Published: February 2017

PURPOSE

To assess the performance and the potential clinical impact of a new antibody imaging agent, CEA-Scan (Immunomedics Inc, Morris Plains, NJ), in 210 presurgical patients with advanced recurrent or metastatic colorectal carcinomas.

METHODS

CEA-Scan, an anti-carcinoembryonic antigen (CEA) Fab antibody fragment labeled with technetium-99m-pertechnetate (99mTc), was injected intravenously (IV), and external scintigraphy was performed 2 to 5 and 18 to 24 hours later. Imaging with conventional diagnostic modalities (CDM) was also performed, and findings were confirmed by surgery and histology.

RESULTS

The sensitivity of CEA-Scan was superior to that of CDM in the extrahepatic abdomen (55% v 32%; P = .007) and pelvis (69% v 48%; P = .005), and CEA-Scan findings complemented those of CDM in the liver. Among 122 patients with known disease, the positive predictive value was significantly higher when both modalities were positive (98%) compared with each alone (68% to 70%), potentially obviating the need for histologic confirmation when both tests are positive. Imaging accuracy also was significantly improved by adding CEA-Scan to CDM. In 88 patients with occult cancer, imaging accuracy was enhanced significantly by CEA-Scan combined with CDM (61% v 33%). Potential clinical benefit from CEA-Scan was demonstrated in 89 of 210 patients. Only two patients developed human antimouse antibodies (HAMA) to CEA-Scan after a single injection, and none of 19 assessable patients after two injections.

CONCLUSION

CEA-Scan affords high-quality, same-day imaging, uses an inexpensive and readily available radio-nuclide, adds clinically significant information in assessing extent and location of disease in colorectal cancer patients, and only rarely induces a HAMA response.
Phase II study of paclitaxel therapy for unresectable biliary tree carcinomas.
Authors: Jones D V , Lozano R , Hoque A , Markowitz A , Patt Y Z
Published: February 2017

PURPOSE

To evaluate the efficacy of paclitaxel administered to patients with unresectable adenocarcinomas of the gallbladder and biliary tree over 3 hours every 21 days.

PATIENTS AND METHODS

Fifteen patients with unresectable and/or metastatic carcinoma of the gallbladder and bile ducts received intravenous paclitaxel over 3 hours after premedication with dexamethasone, diphenhydramine, and cimetidine. Treatment was repeated every 21 days, and one complete course of therapy was comprised of two such 21-day treatment cycles. The initial dose of paclitaxel was 170 mg/m2, and this was elevated to 200 mg/m2 due to tolerance within the initial patient cohort.

RESULTS

All patients were assessable for both toxicity and response: 11 with bile duct cancer and four with gall-bladder carcinoma. Forty-three cycles of therapy were delivered during the trial (median, two), and one patient remains on treatment. No complete or partial responses were noted, although two patients achieved minor responses that lasted 2 and 2+ months, respectively. There were no deaths on this study, and all but one of the patients is still alive. The therapy was well tolerated, and hematologic and mucosal toxic effects were moderate and readily reversible, although significant neuromuscular adverse effects were noted.

CONCLUSION

These findings indicate that paclitaxel, administered on this schedule, is tolerable, but is unlikely to have activity in metastatic carcinomas of the biliary tree. It is unclear whether a different regimen of paclitaxel, or another taxane, may have activity in these neoplasms.
Fertility after chemotherapy for testicular germ cell cancers.
Authors: Lampe H , Horwich A , Norman A , Nicholls J , Dearnaley D P
Published: February 2017

PURPOSE

To analyze the probability of recovery of spermatogenesis after orchidectomy and cisplatin-based chemotherapy (CT) for testicular germ cell cancer.

PATIENTS AND METHODS

One hundred seventy-eight patients treated between 1979 and 1991 were selected by the requirement of sperm count both pre-CT and post-CT. Counts were classified as normospermic (NS) if more than 10 x 10(6)/mL, oligospermic (OS) if 1 to 9 x 10(6)/mL, and azoospermic (AS) if less than 1 x 10(6)/mL. The median follow-up time after CT before sperm analysis was 30 months.

RESULTS

Analysis of 170 patients whose spermatogenesis was reassessed at least 1 year after CT showed that of 89 patients whose pre-CT counts were NS, the post-CT count was NS in 64%, OS in 16%, and AS in 20%. There was clear evidence for continued recovery beyond 1 year; the probability of spermatogenesis increased to 48% by 2 years and 80% by 5 years. There was a significantly higher probability of recovery to OS and NS count levels in the 54 patients treated with carboplatin-rather than cisplatin-based therapy. There was an independent and similar effect of normal pre-CT count. There was a reduced probability to recover to OS in the 26 patients treated with more than four cycles of CT. A prognostic model identified three groups with 25%, 45%, and 82% probabilities of recovering spermatogenesis by 2 years after CT.

CONCLUSION

Analysis of pre-CT sperm count together with details of planned treatment can be used to predict recovery of spermatogenesis following germ cell CT.
Assessment of genomic damage in colorectal cancer by DNA fingerprinting: prognostic applications.
Authors: Arribas R , Capellà G , Tórtola S , Masramon L , Grizzle W E , Perucho M , Peinado M A
Published: February 2017

PURPOSE

Here we evaluate the prognostic significance of the relative value of genomic damage assessed by DNA fingerprinting in colorectal cancer.

MATERIALS AND METHODS

Sixty-three tumor and paired normal mucosa samples were included in the study. Genomic damage was assessed by comparative analysis of paired normal and tumor tissue DNA fingerprints by the arbitrarily primed polymerase chain reaction (AP-PCR). Decreases and increases of intensity in bands were computed and referred to the total number of visualized bands per case. An index reflecting the genomic damage fraction (GDF), with separated values for losses and gains, was obtained for each tumor. This index was used to determine molecular and clinicopathologic correlates after exclusion of eight cases displaying microsatellite instability.

RESULTS

Fifty-five cases were considered for the statistical analysis. The average fraction of altered bands per tumor was 0.287+/-0.121. When losses and gains were computed separately, the average fraction of changes was 0.126+/-0.113 and 0.161+/-0.120, respectively. Tumors lacking a ras mutation showed an increased GDF, primarily because of a higher fraction of gains. Tumors that were at advanced Dukes' stages and that were poorly differentiated also displayed a higher GDF. Finally, disease-free survival was significantly diminished in tumors with a GDF greater than 0.314 (P < .001). The prognostic significance of the GDF was independent of Dukes' stage (Cox multivariate analysis, P = .005).

CONCLUSION

The degree of genomic damage assessed by unbiased DNA fingerprinting correlates with genotypic, phenotypic, and clinical variables in colorectal carcinoma and may be useful in assessing prognosis in colorectal cancer.
Euthanasia and physician-assisted suicide: a comparative survey of physicians, terminally ill cancer patients, and the general population.
Authors: Suarez-Almazor M E , Belzile M , Bruera E
Published: February 2017

PURPOSE AND METHODS

There is an ongoing debate about the legalization of euthanasia. The attitudes and beliefs of the general public and physicians appear to differ; the views of patients have not been adequately explored. During 1995, we conducted a simultaneous survey in the province of Alberta, Canada, of a random sample of 1,240 individuals from the general population, 179 physicians, and 62 consecutive patients with terminal cancer. The same instrument was administered to the public and physicians through telephone interview, and to patients in a face-to-face interview. Statements related to the legalization of euthanasia and physician-assisted suicide were scored using 1-to-7 Likert agreement scales.

RESULTS

A slight majority of members of the public and terminally ill patients (50% to 60%) agreed with the legalization of euthanasia and assisted suicide, while most physicians (60% to 80%) opposed it. In multivariate analysis, independent associations with support of active end of life measures included the following: group surveyed, strength of religious beliefs, religion (highest support by individuals with no religion), education (lower education associated with higher support), and the perception of burden on families, and physical and emotional suffering by cancer patients.

CONCLUSION

In all groups, a marked polarization of attitudes was observed, with most individuals either strongly agreeing or strongly disagreeing with the statements in the survey. Although a slight majority of the public supported euthanasia, one third opposed it. Most physicians opposed these interventions and appeared not to be willing to perform these procedures if legalized. Our findings suggest that legalization at this time could be highly divisive and controversial from a societal perspective.
Treatment of refractory chronic lymphocytic leukemia with fludarabine phosphate via the group C protocol mechanism of the National Cancer Institute: five-year follow-up report.
Authors: Sorensen J M , Vena D A , Fallavollita A , Chun H G , Cheson B D
Published: February 2017

PURPOSE

To provide fludarabine to physicians for the management of patients with advanced refractory chronic lymphocytic leukemia (CLL) and to determine the response rate and duration, toxicity, and survival with this agent.

PATIENTS AND METHODS

This phase II protocol was open to all eligible patients whose local physicians obtained written permission from the National Cancer Institute (NCI) to register patients onto this protocol. Of 791 national and international enrolled patients, 724 with a median age of 65 years received fludarabine, of which 703 were assessable for response.

RESULTS

Thirty-two percent of assessable patients responded (95% confidence interval [CI], 29% to 36%), with 21 patients (3%) obtaining a complete response and 205 (29%) a partial response. The median duration of response was 13.1 months and the median survival time from registration was 12.6 months. Age, performance status (PS), and Rai stage correlated with survival (P < .01). Grade 4 hematologic toxicity was reported in 43% and was associated with infection in 22%. Neurotoxicity (primarily grade 1 motor dysfunction) was reported in 14% patients and correlated with age.

CONCLUSION

This study describes the toxicity and activity of fludarabine in refractory CLL in a setting that more closely resembles clinical practice than most published trials. The low response rate may be related to advanced stage (89% Rai high-risk), disease-related symptoms (63% had B symptoms), and/or degree of prior treatment. Other contributing factors inherent in a group C treatment protocol included lack of central pathology review, variable supportive care, and a tendency to use this mechanism at a later stage in the disease.
Economic and policy implications of adopting paclitaxel as first-line therapy for advanced ovarian cancer: an Ontario perspective.
Authors: Elit L M , Gafni A , Levine M N
Published: February 2017

PURPOSE

To determine the potential economic and policy implications that result from incorporating paclitaxel into first-line therapy for stage 3 and 4 ovarian cancer patients in the province of Ontario, Canada.

METHODS

A cost-effectiveness analysis was conducted to compare cisplatin/cyclophosphamide (CC), a standard therapy, with cisplatin/paclitaxel (CT). Based on survival curves from a clinical trial, mean costs and survival were calculated. Sensitivity analyses were conducted based on altering the duration of paclitaxel infusion, discount rates, and efficacy of paclitaxel.

RESULTS

The mean survival duration is prolonged from 2.06 years with the standard therapy to 2.44 years with the paclitaxel combination. The paclitaxel therapy is more expensive, with a mean cost of $17,469 (Canadian) per patient treated with CT compared with $5,228 per patient with CC. The incremental cost-effectiveness ratio is $32,213 per year gained. Sensitivity analyses show that the conclusions remain unchanged. The use of CT as first-line treatment for advanced ovarian cancer patients in Ontario requires an additional $9 million per year over and above the present costs to treat this patient population.

CONCLUSION

Although paclitaxel-based therapy prolongs survival, it comes at an increased cost. It may not be possible to fund paclitaxel treatment using resources presently allocated to first-line chemotherapy for advanced ovarian cancer. The policy implications for absorbing the cost of paclitaxel in the context of a publicly funded health care system are discussed.
Prospective randomized placebo-controlled study of granulocyte-macrophage colony-stimulating factor without stem-cell transplantation after high-dose melphalan in patients with multiple myeloma.
Authors: Moreau P , Fiere D , Bezwoda W R , Facon T , Attal M , Laporte J P , Colombat P , Haak H L , Monconduit M , Lockhorst H , Girault D , Harousseau J L
Published: February 2017

PURPOSE

To evaluate the impact of granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo on the durations of intravenous (IV) antibiotic use, hospitalization, neutropenia, and fever, as well as remission rates, after high-dose melphalan (HDM) without stem-cell transplantation (SCT) in patients with multiple myeloma (MM).

PATIENTS AND METHODS

One hundred two patients with high-risk MM were randomized 2:1 in a prospective multicenter trial to receive 5 microg/kg/d GM-CSF (69 patients) or placebo (33 patients) starting the day after 140 mg/m2 IV melphalan for up to 21 days.

RESULTS

GM-CSF significantly reduced neutropenia after HDM (median, 23.5 v 29 days; P = .0468), with a trend to reduce the duration of hospitalization (median, 32 v 38 days; P = .0841). Nevertheless, GM-CSF did not significantly reduce infectious toxicity as regards the number of days with fever (median, 5 v 3; P = .359), the number of days with IV antibiotics (median, 22 v 27; P = .14), or early deaths, with an 11.5% treatment-related mortality rate in the GM-CSF group (eight of 69 v two of 32 patients in the placebo group; P = .686). There was no difference in response rates between the two groups of patients.

CONCLUSION

GM-CSF after HDM without SCT is feasible and significantly shortens neutropenia with a trend toward reduction of hospitalization duration, but does not significantly reduce the morbidity and mortality of such therapy. Thus, when intensive therapy is indicated, given that the mortality of HDM followed by SCT reported in the literature is less than 5% and patients are discharged at approximately day 15, despite the risk of contamination by clonogenic malignant cells, SCT appears to be preferable to GM-CSF after HDM.
Phase I trial of docetaxel and cisplatin in previously untreated patients with advanced non-small-cell lung cancer.
Authors: Millward M J , Zalcberg J , Bishop J F , Webster L K , Zimet A , Rischin D , Toner G C , Laird J , Cosolo W , Urch M , Bruno R , Loret C , James R , Blanc C
Published: February 2017

PURPOSE

To determine the maximum-tolerated doses (MTDs), principal toxicities, and pharmacokinetics of the combination of docetaxel and cisplatin administered every 3 weeks to patients with advanced non-small-cell lung cancer (NSCLC) who have not received prior chemotherapy and to recommend a dose for phase II studies.

PATIENTS AND METHODS

Patients with advanced NSCLC and performance status 0 to 2 who had not received prior chemotherapy received docetaxel over 1 hour followed by cisplatin over 1 hour with hydration. Dose levels studied were (docetaxel/cisplatin) 50/75, 75/75, 75/100, and 100/75 mg/m2 repeated every 3 weeks. Colony-stimulating factor (CSF) support was not used. Pharmacokinetics of docetaxel and cisplatin were studied in the first cycle of therapy. Most patients (79%) had metastatic disease or intrathoracic recurrence after prior radiation and/or surgery.

RESULTS

Of 24 patients entered, all were assessable for toxicity and 18 for response. The MTD schedules were docetaxel 75 mg/m2 with cisplatin 100 mg/m2 (dose-limiting toxicities [DLTs] in five of six patients), and docetaxel 100 mg/m2 with cisplatin 75 mg/m2 (DLTs in two of two patients, including one fatal toxicity). Limiting toxicities were febrile neutropenia and nonhematologic, principally diarrhea and renal. Two patients had neutropenic enterocolitis. Pharmacokinetics of both drugs were consistent with results from single-agent studies, which suggests no major pharmacokinetic interaction. Neutropenia was related to docetaxel area under the plasma concentration-versus-time curve (AUC). An alternative schedule was investigated, with cisplatin being administered over 3 hours commencing 3 hours after docetaxel, but toxicity did not appear to be less. Independently reviewed responses occurred in eight of 18 patients (44%; 95% confidence interval, 22% to 69%), most following 75 mg/m2 of both drugs.

CONCLUSION

Docetaxel 75 mg/m2 over 1 hour followed by cisplatin 75 mg/m2 over 1 hour is recommended for phase II studies. The responses seen in this phase I study suggest a high degree of activity of this combination in previously untreated advanced NSCLC.
Six cycles of ABVD in the treatment of stage I and II Hodgkin's lymphoma: a pilot study.
Authors: Rueda A , Alba E , Ribelles N , Sevilla I , Ruiz I , Miramón J
Published: February 2017

PURPOSE

Chemotherapy is the standard treatment in advanced Hodgkin's lymphoma and a therapeutic alternative for early stages. Although polychemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is equivalent or superior to mechloretamine, vincristine, procarbazine, and prednisone (MOPP) in advanced disease, no series have been published using ABVD without associated radiotherapy in early stages. We report the results obtained with the administration of six cycles of ABVD alone in clinical stage I and II disease.

PATIENTS AND METHODS

From January 1990 to October 1994, 23 patients with stage I or II Hodgkin's lymphoma were treated with six cycles of ABVD; six patients who met the criteria for mediastinal bulky disease also received radiotherapy to the mediastinum.

RESULTS

After six cycles, 20 complete responses (CRs) and three partial responses (PRs), which became CRs after radiotherapy, were obtained. Toxicity was moderate and manageable. With a median follow-up duration of 37 months (range, 12 to 75), three patients have relapsed and one has died. Overall and progression-free survival rates at 42 months are 95% and 84%, respectively.

CONCLUSION

Six cycles of ABVD are effective and safe in the treatment of stage I and II Hodgkin's lymphoma, at least in the short term, but long-term observation data are not yet available.
Detection of relapse in early-stage Hodgkin's disease: role of routine follow-up studies.
Authors: Torrey M J , Poen J C , Hoppe R T
Published: February 2017

PURPOSE

To examine the costs and benefits of routine follow-up evaluation in patients treated with radiation therapy for early-stage Hodgkin's disease.

PATIENTS AND METHODS

We retrospectively examined patterns of follow-up evaluation and methods of relapse detection among 709 patients with stage I and II Hodgkin's disease treated with primary radiotherapy between 1969 and 1994. We determined the probability of relapse detection for seven routine follow-up procedures, compared their relative costs, and determined the impact of each procedure on the likelihood of survival following salvage therapy.

RESULTS

Relapse has occurred in 157 patients (22%) at a median 1.9 years (range, 0 to 13 years) posttreatment. Relapse was suspected primarily by history (Hx) in 55% of patients, physical examination (PE) in 14%, chest x-ray (CXR) in 23%, and abdominal x-ray (KUB) in 7%. Only one relapse (1%) was identified by a routine laboratory study. The rate of relapse detection was highest for a combination of Hx and PE (78 of 10,000 examinations) followed by CXR (26 of 10,000 examinations). The projected charges (1995 dollars) per relapse detected by routine follow-up Hx and PE were $11,000 compared with $68,000 for CXR and $142,000 for KUB. The 10-year actuarial survival rate following salvage therapy was 65% overall, 65% for patients in whom relapse was detected by Hx or PE, and 69% for patients in whom relapse was detected by radiographs (P = not significant).

CONCLUSION

The majority of relapses occurred within 5 years of treatment and were identified by Hx and PE. CXR was useful during the first 3 years of follow-up evaluation. KUB, CBC, and laboratory studies accounted for nearly half of all follow-up charges and rarely led to the detection of relapse. Their routine use as a method of relapse detection is questionable. In general, the method of relapse detection did not have a significant impact on the likelihood of successful salvage therapy.
Phase I trial of PN401, an oral prodrug of uridine, to prevent toxicity from fluorouracil in patients with advanced cancer.
Authors: Kelsen D P , Martin D , O'Neil J , Schwartz G , Saltz L , Sung M T , von Borstel R , Bertino J
Published: February 2017

PURPOSE

We performed a phase I study to determine the appropriate dose of PN401, a uridine (URD) prodrug, to use as a rescue agent for fluorouracil (FU) and than to determine the maximum-tolerated dose (MTD) of FU when given with PN401.

PATIENTS AND METHODS

Patients with advanced cancer received oral PN401 as either a suspension or a tablet in escalating doses. A pharmacokinetic analysis was performed to determine which dose best achieved a target value of sustained levels of URD > or = 50 mumol/L. In the first phase of the study, all patients received a fixed dose of FU 600 mg/m2 as a rapid intravenous bolus followed by 10 doses of PN401 given at 6-hour intervals. PN401 therapy commenced 24 hours after FU. After determination of the appropriate dose of PN401, a second group of patients received escalating doses of FU with a fixed dose of PN401.

RESULTS

Thirty-eight patients with advanced cancer received PN401 and FU. Pharmacokinetic analysis indicated that either 6.6 g of PN401 as an oral suspension or 6 g given in tablet form resulted in high bioavailability of URD, with sustained plasma concentrations greater than 50 mumol/L. In the second phase of the study, FU doses were escalated from 600 to 1,000 mg/m2. FU was given as a rapid intravenous bolus weekly for 6 weeks with a 2-week rest. The MTD of FU given in this fashion with PN401 rescue was 1,000 mg/m2, at which level two of six patients had neutropenic fever. FU at doses of 800 mg/m2 for 6 weeks was well tolerated without significant toxicity when given with PN401 rescue.

CONCLUSION

Oral PN401 is well tolerated and total doses of 6 g every 6 hours yield sustained levels of URD in the target range of 50 mumol/L. The MTD of FU with PN401 rescue is 1,000 mg/m2 and the recommended dose for phase II trials is 800 mg/m2 given weekly for 6 weeks with dose escalation. Further studies to define better the appropriate interval for PN401 rescue and the appropriate dose of FU when given with biochemical modulation, such as with leucovorin, are indicated.
Phase II multicenter study of human CD52 antibody in previously treated chronic lymphocytic leukemia. European Study Group of CAMPATH-1H Treatment in Chronic Lymphocytic Leukemia.
Authors: Osterborg A , Dyer M J , Bunjes D , Pangalis G A , Bastion Y , Catovsky D , Mellstedt H
Published: February 2017

PURPOSE

CAMPATH-1H is a human immunoglobulin G1 (IgG1) anti-CD52 monoclonal antibody (MAb) that binds to nearly all B- and T-cell lymphomas and leukemias. We report the results of a multicenter phase II trial that used CAMPATH-1H in previously chemotherapy-treated patients with chronic lymphocytic leukemia (CLL).

MATERIALS AND METHODS

Twenty-nine patients who had relapsed after an initial response (n = 8) or were refractory (n = 21) to chemotherapy were treated with CAMPATH-1H administered as a 30-mg 2-hour intravenous (IV) infusion thrice weekly for a maximum period of 12 weeks.

RESULTS

Eleven patients (38%) achieved a partial remission (PR) and one (4%) a complete remission (CR) (response rate, 42%; 95% confidence interval [CI], 23% to 61%). Three of eight patients (38%) with a relapse and nine of 21 refractory patients (43%) responded to CAMPATH-1H therapy. CLL cells were rapidly eliminated from blood in 28 of 29 patients (97%). CR in the bone marrow was obtained in 36% and splenomegaly resolved completely in 32%. Lymphadenopathy was normalized in only two patients (7%). The median response duration was 12 months (range, 6 to 25+). World Health Organization (WHO) grade IV neutropenia and thrombocytopenia developed in three (10%) and two patients (7%), respectively. Neutropenia and thrombocytopenia recovered in most responding patients during continued CAMPATH-1H treatment. Lymphopenia (< 0.5 x 10(9)/L) occurred in all patients. Two patients had opportunistic infections and four had bacterial septicemia.

CONCLUSION

CAMPATH-1H had significant activity in patients with advanced and chemotherapy-resistant CLL. The most pronounced effects were noted in blood, bone marrow, and spleen. Preferential clearance of blood may allow harvesting of uncontaminated blood stem cells for use in high-dose chemotherapy protocols.
Mobilization and transplantation of Philadelphia-negative peripheral-blood progenitor cells early in chronic myelogenous leukemia.
Authors: Carella A M , Cunningham I , Lerma E , Dejana A , Benvenuto F , Podestà M , Celesti L , Chimirri F , Abote M , Vassallo F , Figari O , Parodi C , Sessarego M , Valbonesi M , Carlier P , Prencipe E , Gatti A M , van den Berg D , Hoffman R , Frassoni F
Published: February 2017

PURPOSE

Mobilization of Philadelphia (Ph) chromosome-negative progenitors is now possible in many Ph1-positive chronic myelogenous leukemia (CML) patients who had received interferon alfa (IFN-alpha) with no cytogenetic response. In this pilot study, we used this approach in patients without prior IFN-alpha therapy to determine if the number and quality of mobilized progenitors would be increased and to evaluate the potential effect of these cells as autografts.

PATIENTS AND METHODS

Twenty-two untreated patients were mobilized within 12 months of diagnosis. The treatment regimen consisted of the mini-ICE protocol. Beginning on day +8, granulocyte colony-stimulating factor (G-CSF) was used in all patients. Leukophoresis was performed as the patients were recovering from aplasia, when WBC count exceeded 0.8 x 10(9)/L.

RESULTS

In 14 patients, (63%) the leukophoresis product was entirely Ph1-negative and in four patients the Ph1-positive cell rate was < or = 7%. Significant numbers of long-term culture-initiating cells (LTC-IC) and CD34+ Thy1+Lin- cells were found in most of the Ph1-negative collections that were tested. Twelve patients underwent autografting with their mobilized peripheral-blood progenitor cells (PBPC) (Ph1-negative collections, 10 patients; major cytogenetic response, two patients). All patients engrafted and are alive; six have Ph1-negative marrow 7 to 15 months after autografting. Posttransplant treatment was IFN-alpha combined with interleukin (IL)-2 because of the recent demonstration of synergistic activity in augmenting cytolytic activity.

CONCLUSION

Intensive chemotherapy given in early chronic phase of CML is well tolerated and results in high numbers of circulating Ph1-negative precursor cells.
Role of a second transplant in the management of poor-prognosis lymphomas: a report from the European Blood and Bone Marrow Registry.
Authors: Vandenberghe E , Pearce R , Taghipour G , Fouillard L , Goldstone A H
Published: February 2017

PURPOSE

Treatment of selected patients with poor-prognosis lymphomas with high-dose chemotherapy and marrow or peripheral stem-cell rescue improves prognosis. A second course of myeloablative chemotherapy has been given to some patients, but few data are available on the indications, morbidity, and overall survival associated with this approach. This study was undertaken to evaluate morbidity and identify subgroups of patients who may benefit from a second transplant.

PATIENTS AND METHODS

Thirty-four patients with lymphoma given two cycles of myeloablative chemotherapy and entered onto the European Blood and Bone Marrow Transplant (EBMT) registry between 1982 and 1995 were included in this study: Hodgkin's disease (HD), n = 12; intermediate/high-grade non-Hodgkin's lymphoma (HG-NHL), n = 17; and low-grade non-Hodgkin's lymphoma (LG-NHL), n = 5. The reason for second transplant, status at transplant, conditioning regimen, morbidity, and both progression-free survival (PFS) and overall survival (OS) were assessed.

RESULTS

The second procedure was performed for the following reasons: (1) elective double procedure in four patients, (2) relapse after first transplant in 20, (3) partial remission (PR) after first transplant in eight, and (4) refractory disease after first transplant in two. The OS rate at 2 years for patients who underwent two transplants (estimated from the date of second transplant) was 49%, with a median follow-up time of 44 months. The OS rate at 2 years by histologic subtype was as follows; HD, 50%; HG-NHL, 60%; and LG-NHL, 0%. Seven of 15 patients with HD or HG-NHL who relapsed after they had achieved a posttransplant complete remission (CR) remain in CR 13 to 36 months after the second transplant, compared with two of 10 patients in CR (at 6 and 19 months after second transplant) who achieved a PR or had refractory disease after the first transplant. There were eight deaths (24%) before 3 months, of which three (9%) were transplant-related and the remainder due to persistent disease. Three late toxic deaths occurred: two of cardiovascular disease and one of secondary leukemia.

CONCLUSION

Selected patients with HD and HG-NHL whose disease recurs after one transplant may benefit from a second transplant. Patients with refractory disease and LG-NHL did not benefit from a second transplant.
Early restaging gallium scans predict outcome in poor-prognosis patients with aggressive non-Hodgkin's lymphoma treated with high-dose CHOP chemotherapy.
Authors: Janicek M , Kaplan W , Neuberg D , Canellos G P , Shulman L N , Shipp M A
Published: February 2017

PURPOSE

This prospective study assessed the predictive value of early restaging gallium (Ga) and computed tomographic (CT) scans in poor-prognosis patients with aggressive non-Hodgkin's lymphoma (NHL) who were treated with high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy.

PATIENTS AND METHODS

Thirty newly diagnosed patients with bulky (> or = 10 cm) advanced-stage aggressive NHL were treated with a four-cycle high-dose CHOP regimen (22 patients at maximum-tolerated dose [MTD]: cyclophosphamide 4 g/m2, doxorubicin 70 mg/m2, vincristine 2 mg, and prednisone 100 mg orally for 5 days). All patients had chest/abdominal/pelvic CT scans and 10-mCi Ga scans at baseline and following two and four cycles of therapy. Scans were reviewed in a blinded manner for CT-documented rates of response and sizes of residual masses and Ga avidity of residual masses. The results of early (post-cycle 2) and final (post-cycle 4) restaging were subsequently associated with clinical outcome.

RESULTS

CT-documented rates of response and residual mass sizes were indistinguishable in complete responders who remained continuously disease-free (CR-Cont), complete responders who subsequently relapsed (CR-Rel), and partial responders who then progressed (PR/Prog). In marked contrast, early restaging (post-cycle 2) Ga scans accurately delineated these three categories of patients: CR-Cont 90% Ga-negative (18 of 20 patients) versus CR-Rel 25% Ga-negative (one of four patients) versus PR/Prog 0% Ga-negative (zero of six patients) (P = .000014). At a median follow-up duration of 31 months (range, 21 to 46), 94% of patients who had negative early restaging Ga scans remain free from progression (FFP), whereas only 18% of patients who had positive early restaging Ga scans remain FFP (P = .000007). Early restaging Ga scans were more predictive for FFP than final restaging Ga scans because patients who required four full cycles of therapy to become Ga-negative were more likely to develop recurrent disease.

CONCLUSION

Early restaging Ga scans delineate patients who are likely to have prolonged disease-free survival from those who fail to respond to intensive induction therapy. Patients whose tumors remain Ga-positive midway through high-dose CHOP therapy have a poor outcome and may be candidates for alternative treatment.
Comparative diagnostic accuracy of magnetic resonance imaging and immunoscintigraphy for detection of bone marrow involvement in patients with malignant lymphoma.
Authors: Altehoefer C , Blum U , Bathmann J , Wüstenberg C , Uhrmeister P , Laubenberger J , Lange W , Schwarzkopf J , Moser E , Langer M
Published: February 2017

PURPOSE

To compare the diagnostic accuracy of magnetic resonance imaging (MRI) and immunoscintigraphy (IS) for detection of bone marrow infiltration in malignant lymphoma.

PATIENTS AND METHODS

In 32 patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL), MRI of the axial skeleton and whole-body IS using technetium-99m (99mTc)-labeled monoclonal antibodies were reviewed and compared with iliac crest biopsies. Criterion for marrow infiltration was a positive biopsy or concordant positive results of MRI and IS.

RESULTS

In 16 patients (50%), MRI, IS, and iliac crest biopsies were negative for marrow infiltration. Iliac crest biopsy showed infiltration in only four patients (13%). Infiltration was missed in two of 32 patients with IS and in one patient with MRI. In one additional patient, MRI was false-positive because of pelvic hematopoietic hyperplasia. A subset of nine patients (28%) with negative biopsies had bone marrow involvement according to MRI and IS with identical location and pattern of infiltration. In eight of these nine patients, diagnostic imaging indicated marrow involvement only in noncrest marrow. Subsequent biopsy confirmed infiltration in five patients. The clinical course suggested true-positive imaging results in the remaining four patients. Two patients (6%) remained equivocal. Overall concordance of MRI and IS for marrow infiltration was 88% (28 of 32 patients).

CONCLUSION

Diagnostic imaging is essential for optimal staging in malignant lymphoma, as blind biopsies appear to have low sensitivity for bone marrow infiltration because of frequent involvement in noncrest marrow. both imaging modalities show a high rate of detection of bone marrow infiltration.
Importance of bleomycin in combination chemotherapy for good-prognosis testicular nonseminoma: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group.
Authors: de Wit R , Stoter G , Kaye S B , Sleijfer D T , Jones W G , ten Bokkel Huinink W W , Rea L A , Collette L , Sylvester R
Published: February 2017

PURPOSE

This prospective randomized trial was designed to compare the efficacy of etoposide plus cisplatin (EP) versus bleomycin, etoposide, and cisplatin (BEP) chemotherapy in patients with good-prognosis metastatic nonseminomatous testicular cancer.

PATIENTS AND METHODS

Four hundred nineteen patients with good-prognosis nonseminomatous testicular cancer were randomized to receive four cycles of cisplatin 20 mg/m2 on days 1 to 5 plus etoposide 120 mg/m2 on days 1, 3, and 5 with or without bleomycin 30 mg weekly.

RESULTS

Of 395 eligible patients, 169 of 195 patients allocated to EP (87%) and 189 of 200 patients allocated to BEP (95%) achieved a complete response with chemotherapy alone or after postchemotherapy surgery. These results are significantly different (P = .0075). After a median follow-up duration of 7.3 years, eight patients (4%) on each treatment arm relapsed. In view of the low number of unfavorable treatment outcomes (11%), no significant differences were detected in time to progression (P = .136) and survival (P = .262). Both the acute and late pulmonary toxicity and neurotoxicity were significantly greater in patients who received BEP, whereas Raynaud's phenomenon occurred exclusively in patients who received BEP (P < .001). Two patients treated with BEP died of bleomycin pulmonary toxicity.

CONCLUSION

BEP is the most effective combination regimen in the treatment of disseminated nonseminomatous germ cell cancer. In this particular BEP regimen with etoposide at a dose of 360 mg/m2 per cycle, even in good-prognosis patients, bleomycin cannot be deleted without compromising treatment efficacy, but its use is associated with more toxicity (particularly pulmonary) and efforts to reduce this merit further exploration.
High-dose chemotherapy with autologous hematopoietic stem-cell support for breast cancer in North America.
Authors: Antman K H , Rowlings P A , Vaughan W P , Pelz C J , Fay J W , Fields K K , Freytes C O , Gale R P , Hillner B E , Holland H K , Kennedy M J , Klein J P , Lazarus H M , McCarthy P L , Saez R , Spitzer G , Stadtmauer E A , Williams S F , Wolff S , Sobocinski K A , Armitage J O , Horowitz M M
Published: February 2017

PURPOSE

To identify trends in high-dose therapy with autologous hematopoietic stem-cell support (autotransplants) for breast cancer (1989 to 1995).

PATIENTS AND METHODS

Analysis of patients who received autotransplants and were reported to the Autologous Blood and Marrow Transplant Registry. Between January 1, 1989 and June 30, 1995, 19,291 autotransplants were reviewed; 5,886 were for breast cancer. Main outcomes were progression-free survival (PFS) and survival.

RESULTS

Between 1989 and 1995, autotransplants for breast cancer increased sixfold. After 1992, breast cancer was the most common indication for autotransplant. Significant trends included increasing use for locally advanced rather than metastatic disease (P < .00001) and use of blood-derived rather than marrow-derived stem cells (P < .00001). One-hundred-day mortality decreased from 22% to 5% (P < .0001). Three-year PFS probabilities were 65% (95% confidence intervals [Cls], 59 to 71) for stage 2 disease, and 60% (95% Cl, 53 to 67) for stage 3 disease. In metastatic breast cancer, 3-year probabilities of PFS were 7% (95% Cl, 4 to 10) for women with no response to conventional dose chemotherapy; 13% (95% Cl, 9 to 17) for those with partial response; and 32% (95% Cl, 27 to 37) for those with complete response. Eleven percent of women with stage 2/3 disease and less than 1% of those with stage 4 disease participated in national cooperative group randomized trials.

CONCLUSION

Autotransplants increasingly are used to treat breast cancer. One-hundred-day mortality has decreased substantially. Three-year survival is better in women with earlier stage disease and in those who respond to pretransplant chemotherapy.
Gemcitabine versus the combination of cisplatin and etoposide in patients with inoperable non-small-cell lung cancer in a phase II randomized study.
Authors: Perng R P , Chen Y M , Ming-Liu J , Tsai C M , Lin W C , Yang K Y , Whang-Peng J
Published: February 2017

PURPOSE

A phase II randomized study was conducted to evaluate the efficacy and toxicity of gemcitabine (GEM) versus the combination of cisplatin and etoposide (EP) in Chinese patients with inoperable (stage III or IV) non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS

From March 1995 to February 1996, 53 patients were enrolled onto the study: 27 onto the GEM arm and 26 onto the EP arm. In the GEM arm, gemcitabine 1,250 mg/m2 was given as a 30-minute intravenous (i.v.) infusion on days 1, 8, and 15 of each 28-day cycle. In the EP arm, cisplatin 80 mg/m2 was given on day 1 and etoposide 80 mg/m2 was given on days 1, 2, and 3 of each 28-day cycle.

RESULTS

Twenty-six patients are assessable for treatment response on the GEM arm and 24 on the EP arm. Five patients (19.2%) on the GEM arm and five patients (20.8%) on the EP arm achieved a partial response (PR). No complete responses were attained on either treatment arm. All patients enrolled onto the study were eligible for toxicity assessment. The main toxicities were myelosuppression and vomiting, which included World Health Organization (WHO) grade 3 or 4 leukopenia (3.7%), thrombocytopenia (7.4%), anemia (7.4%), and nausea/vomiting (3.7%) on the GEM arm, and WHO grade 3 or 4 leukopenia (30.8%), thrombocytopenia (7.7%), anemia (15.4%), and nausea/vomiting (34.6%) on the EP arm. The median survival time was 37 weeks on the GEM arm and 48 weeks on the EP arm.

CONCLUSION

Gemcitabine is a well-tolerated chemotherapeutic agent for NSCLC. The antitumor activity was promising, with a 19.2% single-drug response rate, when compared with EP combination chemotherapy, which had a response rate of 20.8%. The safety profile is better than that of EP treatment.
Prevention of acute emesis in cancer patients following high-dose cisplatin with the combination of oral dolasetron and dexamethasone.
Authors: Kris M G , Pendergrass K B , Navari R M , Grote T H , Nelson A M , Thomas V , Ferguson B B , Allman D S , Pizzo B A , Baker T W , Fernando I J , Chernoff S B
Published: February 2017

PURPOSE

Dolasetron is a 5-HT3 antagonist antiemetic with active oral and intravenous formulations. The effects of this class are enhanced when combined with dexamethasone. This study tested the ability of the combination of oral dolasetron 200 mg and oral dexamethasone 20 mg to prevent acute emesis in cancer patients receiving initial cisplatin at doses > or = 70 mg/m2. Additionally, patients were randomly assigned to receive a second dosage of the regimen 16 hours later to improve control of acute symptoms.

PATIENTS AND METHODS

A total of 75 patients were entered, with 38 randomized to the two-dose regimen. Thirty-five percent were women and 77% had lung cancer.

RESULTS

Overall, the regimen prevented acute vomiting in 76% (95% confidence interval, 65% to 85%), including 74% of 35 patients who received cisplatin at doses > or = 100 mg/m2. There was no observed difference in emesis prevention between the one-dose (76%) and two-dose (76%) regimens (95% confidence interval for the difference, -20% to 19%). The median time to the onset of emesis was 19 hours for the one-dose regimen and 17 hours for the two-dose regimen in those patients with emesis. Headache occurred in 11% who received one dose and 16% who received two doses.

CONCLUSION

The combination of oral dolasetron 200 mg and dexamethasone 20 mg given only once prevented acute emesis in 76% of patients who received cisplatin > or = 70 mg/m2. Administration of a second dose of the regimen did not improve the observed prevention rate or delay the time to emesis. This one-dose oral regimen has comparable or better effectiveness than reported results of intravenous combination regimens in preventing cisplatin-induced vomiting and merits further study and use.
Engraftment and molecular monitoring of CD34+ peripheral-blood stem-cell transplants for follicular lymphoma: a pilot study.
Authors: McQuaker I G , Haynes A P , Anderson S , Stainer C , Owen R G , Morgan G J , Lumley M , Milligan D , Fletcher J , Bessell E M , Davis J M , Russell N H
Published: February 2017

PURPOSE

A pilot study to validate the use of CD34+ selection (Ceprate SC) of blood stem-cell collection in patients with advanced follicular lymphoma receiving myeloablative chemoradiotherapy.

PATIENTS AND METHODS

Seventeen patients were entered onto the protocol. Thirteen of 17 patients have undergone transplantation; the median age is 42.5 years (range, 33 to 51), seven of 13 are stage IVB, two stage IVA, three stage IIIB, and one stage IIB. All except two patients were treated after first or subsequent relapses after receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy to achieve a good partial (six of 13) or complete (seven of 13) response before stem-cell mobilization with cyclophosphamide 3 g/m2 and filgrastim 300 microg once daily.

RESULTS

Eleven of 13 patients had a detectable t(14;18) by nested polymerase chain reaction (PCR). Median CD34+ count before selection was 2.9 x 10(6)/kg (range, 1.17 to 11.3) and after CD34+ selection was 1.54 x 10(6)/kg (range, 0.88 to 7.6) with a median CD34+ yield of 62.4% (range, 17% to 95%) and purity of 60% (range, 39.3% to 73%). Of the 11 patients known to have t(14;18), 10 had PCR-detectable contamination of stem-cell harvests that became PCR negative in six of the 10 after CD34+ selection. Engraftment was rapid with a median day to absolute neutrophil count (ANC) greater than 0.5 x 10(9)/L of 13 days (range, 11 to 21) and platelet count greater than 20 x 10(9)/L of 14 days (range, 10 to 44). With a median follow-up duration of 15 months, three patients have remained persistently PCR-positive, two of whom received PCR-positive stem cells. Two have relapsed. Of the seven patients who received PCR-negative stem cells, five have had no PCR-detectable disease in posttransplant bone marrow samples.

CONCLUSION

Longer follow-up duration is required to determine the significance of these findings, but we have confirmed the feasibility of CD34+ selected cells to deplete peripheral-blood stem cells of tumor cells from patients undergoing high-dose therapy for follicular lymphoma.