bluuebunny/crossref_metadata_2025 huggingface dataset:
An alternating chemotherapy combination (macoble) for intermediate and high‐grade non‐hodgkin's lymphoma
Authors: Harding M. , McNulty L. , Paul J. , Lee F. , Dunlop D. , Soukop M.
Published: February 2007

From June 1983 to February 1986, 48 patients with intermediate or high‐grade non‐Hodgkin's lymphomas (NHL) received a CHOP based combination with the addition of etoposide on days 1 and 2, bleomycin days 1 and 10 and methotrexate 1.5 g/m2 on day 10 (MACOBLE). Their median age was 59 years, 20 (42 per cent) had an ECOG performance status (PS) of 2 or 3, 24 (50 per cent) had stage IV disease, 25 (52 per cent) B symptoms and 21 (44 per cent) bulk (> 10 cm) disease.

With a median follow‐up of 62 months, 12 patients are alive, 10 of whom are disease‐free. Median overall survival was 13 months (95 per cent confidence interval 6–23 months) with actuarial 5‐year survival of 25 per cent (95 per cent confidence interval 13–37 per cent). Factors associated with inferior survival were ECOG PS 2 or 3 (P = 0.004), B symptoms (P = 0.013) and bulk disease (P = 0.017).

These data suggest that, when treating an unselected patient population, attempts to increase the intensity of first‐line chemotherapy may not improve the outcome.
Increase of serum interleukin‐2 and regression of myeloma after rhGM‐CSF treatment of drug induced bone marrow aplasia
Authors: Bernell Per , Pisa Pavel , Hast Robert , Hansson Mona , Sandstedt Bengt , Stenke Leif
Published: February 2007

Recombinant human granulocyte/macrophage colony‐stimulating factor (rhGM‐CSF) was administered to a patient with multiple myeloma (IgA, stage IIA) who had a chemotherapy‐induced bone marrow aplasia with granulocytopenia complicated by severe pneumonia and septicemia. The rhGM‐CSF was given as i.v. infusions, 300–400 μg daily, for three weeks. The patient responded both hematologically and clinically with improved granulocyte counts and clearance of massive pulmonary infiltrates. We also observed a partial remission of the myeloma with decreasing s‐IgA levels and reduced plasma cell infiltration of the bone marrow during a period of up to four months after the rhGM‐CSF treatment. Immunological studies performed during and after cytokine administration showed an increase in serum interleukin‐2 (IL‐2) levels and HLA‐DR positive T‐lymphocytes indicating an activation of the immune system. It is suggested that rhGM‐CSF induced immunological changes which may have contributed to the partial regression of the myeloma.
Second malignant neoplasms in patients with non hodgkin's lymphoma
Authors: Lishner Michael , Slingerland Joyce , Barr Joseph , Panzarella Tony , Degendorfer Pam , Sutcliffe Simon
Published: February 2007

A retrospective review of the records of 3886 patients with non‐Hodgkin's lymphoma registered at the Princess Margaret Hospital between 1970 and 1985 was undertaken to determine the incidence of second malignant tumours. Three thousand and twenty‐one patients with a minimum documented follow‐up of 6 months from referral were identified for analysis. The overall observed/expected ratio for all cancers in patients with malignant lymphoma was 1, suggesting no increased risk of developing a second malignant neoplasm compared to the general population. When the data were analyzed independently for each tumour site, statistically significant increased risk of developing acute non lymphocytic leukemia (ANLL) (p < 0·001) and carcinoma of the tongue (p < 0·05) were found. An increased risk of lung cancer following lymphoma was detected but was not statistically significant. Survival following diagnosis of ANLL and lung cancer was similar and significantly shorter than that following the diagnosis of other second malignancies. The risk of developing a second primary cancer was significantly related to increasing patient age.
Multicentre combined chemotherapy protocol for large cell advanced non hodgkin's lymphoma
Authors: Dumont J. , Charpy‐Validire P. , Mosseri V. , Gabarre J. , Belanger C. , Turpin F. , Binet J. L. , Dreyfus F. , Fourquet A. , Janvier M. , LeDoussal M. , Missenard V. , Natali J. C. , Raphael M. , Teillet F. , Teillet‐Thiebaud F. , Tulliez M. , Varet B. , Vilcoq J. R. , Asselain B.
Published: February 2007

Between October 1985 and October 1989, 75 previously untreated patients with stage III and IV non Hodgkin's lymphoma, large cell type, were treated with an alternating weekly chemotherapy regimen including the following drugs: week 1: Doxorubicin, vincristine, cyclophosphamide, bleomycin, and intrathecal (i.th.) methotrexate and cytarabine; week 2: Methotrexate with leucovorin rescue; week 3: Doxorubicin, ifosfamide with mesna, etoposide, and i.th. methotrexate and cytarabine; week 4: Methotrexate with leucovorin rescue. Complete responders after three cycles according to this schedule (12 weeks) were given 18 gys cranial irradiation and randomized between one additional cycle or three monthly CHOP (consolidation treatment). Among 66 evaluable patients, 53 achieved a complete remission (CR 80 per cent) and seven a partial remission (11 per cent). There were six failures, and nine early deaths during the initial phase, mostly due to septic problems. Forty‐one of the 53 CR patients (77±3 per cent) have remained free of disease with a median follow‐up of 15 months (1–49). Eight of the 12 relapses occurred during the first year, the four others at 13, 14, 16 and 38 months respectively. The 2‐year survival was 63 per cent for the whole group, and 77 per cent for the CR group. No difference has been observed up until now between the two groups with different consolidation treatment. Therefore, this protocol seems to be able to produce a high rate of complete and durable remission. The analysis of prognostic factors suggests that some high‐risk patients should be considered for intensification therapy with the support of autologous bone marrow transplantation.
Twin‐track studies of ifosfamide and mitoxantrone (I‐M) in recurrent high grade non‐hodgkin's lymphoma and hodgkin's disease
Authors: Child J. A. , Simmons A. V. , Barnard D. L. , Parapia L. , Morgan M. , Grace R. J. , Fletcher J. , Parker D. , Norfolk D. R. , Stone J. , Stuart N. S. A. , Tucker J. , Dovey G. J.
Published: February 2007

Fifty‐seven patients, initially diagnosed as having advanced high grade non‐Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first‐line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three‐weekly intervals. Of 33 patients with NHL evaluable for response, 10 (30 per cent) achieved complete remission and six partial remission, giving an overall response rate of 48 per cent. Two patients subsequently went on to bone marrow transplant (BMT)—one allogeneic and the other autologous. Of 18 patients with HD evaluable for response, seven (39 per cent) achieved complete remission and six partial remission, giving an overall response rate of 72 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. The possibility of increasing the safety of the regimen by increasing the time of infusion to 72 h is discussed. Given the need to offer alternative treatment to patients in these categories, this combination (I‐M) is of value in relapsed patients, especially where options are limited because of previous multi‐drug treatment. Remissions may not be prolonged but allow the effective application of additional intensive treatment including bone marrow transplantation.
Etoposide, ifosfamide and methotrexate combination chemotherapy in patients with aggressive non‐hodgkin's lymphoma after failure of the LNH 84 regimen
Authors: Herbrecht R. , Ortiz S. , Damonte J. C. , Liu K. L. , Maloisel F. , Dufour P. , Bergerat J. P. , Oberling F.
Published: February 2007

We assessed the efficacy of an etoposide, ifosfamide and methotrexate combination therapy (VIM) in 24 patients failing the LNH 84 protocol. Eight of these patients were refractory to the LNH 84 induction regimen, 10 were partial responders and the six remaining attained complete response after LNH 84 induction but relapsed during consolidation therapy or after completing the whole programme. Twenty‐three patients were evaluable for response. The VIM regimen provided a 43 per cent complete response rate and an additional 17 per cent partial response rate. The complete response rate was particularly high (67 per cent) in the group of patients who were partial responders to LNH 84 induction treatment. Of the 10 complete responders, five relapsed after 4 to 42 months and five are still alive with no evidence of disease after 27 to 60 months. Overall VIM was well tolerated. Myelotoxicity was the most common side‐effect. Infections with fever were observed in 8 per cent of the VIM courses. This study demonstrates that a complete response and a long survival can be obtained in patients after failure of a high‐dose doxorubicin containing front‐line treatment.
VIM3‐ARA C: An effective salvage regimen in refractory or recurrent aggressive non hodgkin's lymphoma. A report on 18 cases
Authors: Dupriez Brigitte , Morel Pierre , Fenaux Pierre , Colcher‐Plantier Isabelle , Facon Thierry , Bauters Francis
Published: February 2007

Based on encouraging results of previous combination regimens, we used a combination of VM26, ifosfamide, methylGAG, mitoxantrone (or adriamycin), high‐dose (HD) methotrexate and HD Ara C to treat 18 patients with relapsed or refractory NHL. Front‐line therapy had been in most of them a reinforced CHOP regimen. Twelve patients (67 per cent) responded: there were nine (50 per cent) partial responses (PR) and three (17 per cent) complete remissions (CR). Nine of these 12 responders were grafted (eight autologous. one allogeneic transplants), one relapsed before autograft could be performed and the two remaining patients were excluded from autograft because of positive bone marrow. Five of nine patients remained free of disease after 11 + to 27 + months. Response rate was higher in patients who relapsed ‘off’ therapy (2/3), but CR was also obtained in two refractory NHL and persisted for 11 + and 26+ months, suggesting that VIM3‐ARA C was, at least partially, non‐cross‐resistant with front‐line adriamycin‐containing regimens.
Pediatric non‐hodgkin's lymphoma abdominal presentations: A comparative study between two treatment regimens at the national cancer institute cairo
Authors: Hadi Salah S. Abdel , Taneer Omar M. El , Hussein Mohamed H. , Haddad Alaa El , Badawi Sami El , Mokhtar Nadia , Hamza M. R. , Gad Mawla N. El
Published: February 2007

Abdominal presentations of pediatric NHL are rarely amenable to complete surgical resection. Chemotherapy is the hallmark of treatment for pediatric NHL. Treatment of various types of this disease including intra‐abdominal NHL in children with various protocols have not exceeded 54 per cent two‐year disease‐free survival.

We have attempted to study and compare the effects of two treatment regimen upon two groups of previously untreated children up to the age of 16 years who presented to the Pediatric Oncology Unit at the NCI. The first group included 18 children who presented between 1983 and 1985 and were treated by a modified St Jude regimen: while the second group of patients was comprised of 19 children who presented between 1985 and 1987 and were treated by a multi‐national protocol: the MCP 842.

The two groups will be compared with respect to various patient characteristics, response to therapy and their two‐year disease‐free survival as well as overall survival.
Gastric cancer—surgical approach
Authors: Weese James L. , Nussbaum Michael L.
Published: February 2007

Although the incidence of carcinoma of the stomach has steadily declined over the last 50 years. approximately 23 200 new cases will be diagnosed in the United States this year and 13 700 patients will die. Despite marked improvement in operative techniques, fewer than 20 per cent of those diagnosed with gastric cancer beyond the most superficial levels of invasion will survive for over five years. Gastric tumours spread by local, lymphatic, and aggressive intra‐peritoneal routes as well as hematogenous dissemination. Over 87 per cent of recurrences have local or regional components.

Radiation therapy may decrease local and regional recurrences in those patients with transmural tumours. The neoadjuvant use of etoposide, adriamycin, and platinum may yield complete clinical and pathologic responses in patients found to have ‘unresectable’ tumours. Other chemotherapy regimens have been shown to have some effect on advanced disease and may have a role in the neoadjuvant setting.

Our current recommendations for the treatment of gastric cancer in a controlled trial setting would be neoadjuvant chemotherapy followed by R2 resection, postoperative intraoperative radiation therapy with the possibility of postoperative ± chemotherapy. Hopefully, this aggressive multimodality approach will significantly improve the five year survival for this disease.
Specific cutaneous involvement in Hodgkin's disease
Authors: Tassies Dolors , Sierra Jorge , Montserrat Emilio , Marti Rosa , Estrach Teresa , Rozman Ciril
Published: February 2007

In Hodgkin's disease (HD) specific cutaneous involvement is rare. When it occurs, retrograde lymphatic spread, direct extension from the underlying lymph nodes, and hematogenous dissemination are the mechanisms usually implicated. Among 349 patients with HD diagnosed and followed‐up at our institution from 1969 to 1990, three (0·85 per cent) presented specific cutaneous involvement. In two cases with mixed cellularity subtype, skin lesions displayed histologic features similar to those found in the lymph node. Treatment with combination chemotherapy resulted in rapid disappearance of the lesions in two patients but was ineffective in the third. Previous reports of cutaneous involvement in HD, its differential diagnosis. prognostic significance, and treatment are briefly reviewed.
Failure of IMVP‐16 as second‐line treatment for relapsed or refractory high grade non‐hodgkin's lymphoma
Authors: De Lord C. , Newland A. C. , Linch D. C. , Hudson B. Vaughan , Hudson G. Vaughan
Published: February 2007

The British National Lymphoma Investigation (BNLI) has assessed the use of an IMVP‐16 regimen (ifosfamide, methotrexate, VP‐16) in 46 patients with high grade non‐Hodgkin's lymphoma (NHL) who on first‐line chemotherapy either failed to attain a complete remission or relapsed. Seventeen patients responded to IMVP‐16 but only five (11 per cent) went into a complete remission (CR), 12 (26 per cent) had a partial remission (PR) and 29 (63 per cent) showed no response (NR). CR after IMVP‐16 has been maintained in only one case (36 months). The results of this study imply that the use of this IMVP‐16 protocol as second‐line treatment for patients with recurrent high grade NHL is unsuccessful and alternative salvage regimens should be sought.
Etoposide in combination with intermediate dose cytosine arabinoside (ID ARA C) given with the intention of further myeloablative therapy for the treatment of refractory or recurrent hematological malignancy
Authors: Whelan J. S. , Davis C. L. , Rohatiner A. Z. S. , Leahy M. , Maccallum P. K. , Gupta R. K. , Matthews J. , Norton A. J. , Amess J. A. L. , Lister T. A.
Published: February 2007

Thirty‐four patients with refractory or recurrent high grade non‐Hodgkin's lymphoma (NHL) or acute leukemia were treated with a combination of etoposide, 100 mg/m2 daily, and ara C, 1 g/m2 twice daily, for 5 days (VPARAC). This therapy was given in the anticipation that remissions thus achieved would be ‘consolidated’ with myeloablative therapy supported by bone marrow transplantation (BMT). The complete remission rate (CR) in patients with NHL was 3/18 (17 per cent) with partial responses (PR) seen in a further four patients, giving an overall response rate of 39 per cent. Four patients (three in CR, one in PR) proceeded to the planned consolidation treatment. Complete remission was achieved in 2/8 (25 per cent) patients with acute myelogenous leukemia (AML) and in 2/8 patients with acute lymphoblastic leukemia (ALL). Three of these patients subsequently had myeloablative consolidation therapy with BMT. There were four treatment‐related deaths (NHL, two; AML, one; ALL, one). In poor risk patients with high grade NHL and acute leukemia, VPARAC is an effective remission induction programme in 21 per cent of patients. Seven of the original 34 patients received the intended ‘curative’ therapy, of whom only four are alive and well 1 year later.
A new monoclonal antibody which binds to the cytoplasm of large cell lymphomas
Authors: Nakamura Naoya , Suzuki Sayuri , Ono Nobutaka , Tominaga Kunihiko , Hojo Hiroshi , Abe Masafumi , Wakasa Haruki
Published: February 2007

We reported a new monoclonal antibody, designated FUB‐1, reacting with normal and neoplastic large lymphoid cells. FUB‐1 was produced using a Burkitt's lymphoma cell line (HBL‐5) as an immunogen. Its immunoglobulin subtype was IgM. The determinant was not on the surface but in the cytoplasm. Western blotting analysis revealed that the molecular weight of the antigen was 52000 dalton. In the normal lymphoid tissue, FUB‐1 reacted with large lymphoid cells, but not with small or medium‐sized lymphoid cells or plasma cells. In addition, the FUB‐1 antigen was not found in resting cells in the peripheral blood (PB), but it was induced on mononuclear cells of PB by addition of PWM or PMA. In the B‐cell lymphomas tested, FUB‐1 reacted with small cleaved cell lymphomas (3/12), large cell lymphomas (7/10), Burkitt's lymphomas (4/4) and immunoblastic lymphomas (2/2), but not with small cell lymphomas (0/3) or intermediate lymphocytic lymphomas (0/8). These findings indicate that the FUB‐1 antigen appears to be expressed on normal lymphoid cells during blastoid transformation and on neoplastic large lymphoid cells. FUB‐1 also reacted with normal glandular epithelium and various adenocarcinomas.

FUB‐1 may be useful to investigate the mechanism of in vitro blastoid transformation or activation of lymphoid cells.
Intensive retreatment of adults and children with acute lymphoblastic leukemia
Authors: Bassan Renato , Cornelli Pier Emilio , Battista Raffaele , Terzi Fausto , Buelli Maurizio , Rambaldi Alessandro , Viero Piera , D'Emilio Anna , Dini Enrico , Barbui Tiziano
Published: February 2007

Twenty‐three patients (16 adults) failing their first or subsequent (n= 8) intensive treatment for de novo acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia lymphoid blast phase (n = 2) were managed with protocol POG 8201, originally introduced in relapsed ALL of childhood. In this programme, a four‐drug induction phase is followed by early consolidation with teniposide‐cytarabine, intrathecal chemotherapy, continuation weekly chemotherapy alternating teniposide‐cytarabine with vincristine‐cyclophosphamide. and periodic reinduction courses. Fourteen adults and five children with ALL achieved a complete response (CR) (86 per cent). The highest response rate (100 per cent) was obtained in 12 patients treated at first relapse after an initial CR of greater than 18 months (p = 0.07). Median duration of CR was 8 months in adults and 11 months in children. A longer than previous one CR (inversion) was obtained in four cases. Four ALL patients were successfully transplanted from a matched sibling after 3–11 months from achievement of CR. Median overall survival in adults with ALL was 11 months, significantly longer than for 40 comparable cases treated intensively but without rotational continuation therapy in previous years (p< 0.001). This regimen is applicable to adults with relapsed ALL, where prolongation of survival may allow time for effective salvage with bone marrow transplantation.
Comparative pharmacokinetic study of idarubicin and daunorubicin in leukemia patients
Authors: Robert J. , Rigal‐Huguet F. , Hurteloup P.
Published: February 2007

We have studied the pharmacokinetics of idarubicin and daunorubicin in a total of 16 leukemic patients treated with one of these drugs associated with aracytine. The AUCs obtained for unchanged drugs were proportional to the dose, and the dose‐independent pharmacokinetic parameters were very similar for the two drugs: total plasma clearance (39·0L/h/m2 for idarubicin versus 38·6 for daunorubicin), total volume of distribution (1756 versus 1725 L/m2) and elimination half‐life (42·7 versus 47·4 h). The only metabolites detected were the 13–dihydroderivative of each drug, idarubicinol or daunorubicinol. The elimination half‐life of idarubicinol was two times higher than that of daunorubicinol (80·7 versus 37·3 h) which provided an AUC ratio metabolite/parent drug higher for idarubicin than for daunorubicin. In view of the fact that idarubicinol is a much more active metabolite than daunorubicinol, this protracted half‐life metabolite can account for the reported higher activity of idarubicin as compared to daunorubicin.
Intensive chemotherapy for peripheral T‐cell lymphomas
Authors: Liang Raymond , Todd David , Chan T. K. , Chiu Edmond , Lie Albert , Ho Faith C. S. , Loke S. L.
Published: February 2007

Forty‐two patients with previously untreated peripheral T‐cell lymphomas (PTCL) were treated with an intensive chemotherapy protocol. Either the BACOP or the m‐BACOD regimen was used for induction. Patients achieving complete clinical remission after three courses were given intensive consolidation and maintenance chemotherapy similar to the L10/L17M protocol designed by the Memorial Sloan‐Kettering Group for acute lymphoblastic leukemia and lymphoblastic lymphoma. There were 27 (64 per cent) males and 15 (36 per cent) females. The median age was 54 years (mean 53, range 15 to 68). Seven of them (17 per cent) had stage I disease, four (10 per cent) stage II, seven (17 per cent) stage III and 24 (57 per cent) stage IV. Eighteen patients (43 per cent) had B symptoms and four (10 per cent) had bulky disease. According to the Working Formulation, the histology was diffuse mixed in 16 patients (38 per cent), diffuse large cell in 18 (43 per cent), diffuse immunoblastic in four (10 per cent) and unclassifiable in four (10 per cent). According to a modified Japanese Lymphoma Study Group's classification, the histology in 24 patients (57 per cent) was the pleomorphic type, in 13 (31 per cent) immunoblastic‐lymphadenopathy‐like (IBL‐like), and in five (12 per cent) unclassifiable. The overall complete remission rate was 67 per cent. Twenty‐five per cent of the complete responders relapsed and the DFS of the CR patients was 62 per cent at three years. The overall survival of all patients at three years was 52 per cent. Patients with stage I, II and III disease had significantly better CR rate (100 per cent versus 42 per cent, p = 0·001) and overall survival (82 per cent versus 35 per cent at three years, p = 0·01) than those with stage IV disease but the relapse reate and DFS of CR patients were similar. This study shows that the prognosis of patients with PTCL can be improved by intensive therapy.
Bone mineral density (BMD) in patients with lymphoma: The effects of chemotherapy, intermittent corticosteroids and premature menopause
Authors: Ratcliffe Marcia A. , Lanham Susan A. , Reid David M. , Dawson Audrey A.
Published: February 2007

Young women with a chemotherapy‐induced early menopause are theoretically at considerable risk of developing post‐menopausal osteoporosis with problems developing earlier and more severely. In this study bone mineral density (BMD) measurements were made, using a dual‐energy X‐ray absorptiometer (DXA), at the spine and hip of 50 young women who had been treated for lymphoma, 24 of whom were post‐menopausal and 78, healthy age‐matched controls. On analysis of the results, there was no significant difference between the control group and the 26 post‐treatment, pre‐menopausal patients, but the BMD levels were significantly lower than the controls in the post‐menopausal group particularly in 16 patients who had been menopausal greater than 18 months. The results confirm that these young women with treatment‐induced premature menopause are at considerable risk of developing osteoporotic problems. Early recognition of this is important so that preventative measures with hormone replacement therapy can be initiated where this is safely possible. The results also indicate that chemotherapy for lymphoma (cytotoxics and high dose intermittent steroids), are unlikely to contribute directly to the lowering of the BMD of these patients.
Expression of leukocyte adhesion molecules (ICAM‐1/LFA‐1) related to clinical behaviour in B cell lymphomas
Authors: Nozawa Yoshihiro , Yamaguchi Yoshiko , Tominaga Kunihiko , Hojo Hiroshi , Abe Masafumi , Wakasa Haruki
Published: February 2007

We investigated the expression of adhesion molecules of lymphocyte function‐associated antigen‐lα(LFA‐lα) and its ligand intercellular adhesion molecule‐1 (ICAM‐1) on 74 well‐characterized B cell lymphomas. The LFA‐1 was expressed on B cell lymphomas (21/74; 28 percent), but to a lesser degree than ICAM‐1 which was highly expressed (48/74 cases; 64 per cent).

From the results of bone marrow examination of 39 cases with B cell lymphomas, 13 of 16 cases with a lack of ICAM‐1 molecule showed a higher incidence of marrow involvement, but nine of 23 cases with the expression of ICAM‐1 molecule showed a lower incidence.

These findings suggest that the lack of expression of the ICAM‐1 molecule by B cell lymphomas correlates with bone marrow involvement by lymphoma cells (p < 0·05). Expression of the LFA‐1 molecule appears not to correlate with marrow involvement (p < 0·05).
Solitary plasmacytoma of bone: Clinical features, treatment and survival
Authors: Ellis P. A. , Colls B. M.
Published: February 2007

Eleven patients with solitary plasmacytoma of bone were seen between 1978 and 1991. A retrospective review of the clinical features, treatment and survival of these patients was made with the aim of helping to define those at risk for early development of myeloma. Nine patients (82 per cent) had paraparoteinemia at diagnosis. Treatment consisted of local irradiation plus or minus surgery (nine patients) and surgery alone (two patients). No patient received adjuvant chemotherapy. One patient had evidence of both generalized osteopenia and immunoparesis, and progressed to myeloma within six months. Four patients (36 per cent) progressed to myeloma. All of these had paraprotein levels which continued to rise following initial treatment. Three patients died of myeloma at 12, 81 and 144 months and the other patient is alive with myeloma at 6 months. Patients without paraproteinemia at presentation or whose paraprotein decreased after treatment did not progress to myeloma. Three patients have been followed for 8, 11 and 19 years with no evidence of myeloma. Failure of paraprotein to clear after local treatment suggests occult disseminated disease and is predictive of later development of overt myeloma.
Expression of p170 protein in multiple myeloma: A clinical study
Authors: Ucci Giovanni , Petrini Mario , Riccardi Alberto , Invernizzi Rosangela , Carulli Giovanni , Luoni Renata , Giordano Monica , Danova Marco
Published: February 2007

The expression of the p170 multidrug resistance protein by bone marrow plasma cells (BMPC) was assessed at clinical presentation in 53 patients with multiple myeloma (MM) using the C219 monoclonal antibody. Twenty‐two of the 53 (41 per cent) patients had variable aliquots (1–60 per cent, median = 6 per cent) of p170 + BMPC by immunocytochemistry. Five of 10 patients studied using bivariate flow cytometry had both diploid and hyperdiploid (DNA index ranged from 1·2 to 1·5) BMPC with hyperdiploid clones having significantly greater p170 expression than diploid ones. Of the 37 patients evaluated for a response, 20 (54 per cent) had responded to induction chemotherapy. The presence of p170+ BMPC was a negative indicator for achieving response. The response rate was 75 per cent for p170‐ and 25 per cent for p170 + cases (p< 0·01), with no difference on the basis of treatment schedule (melphalan and prednisone, 24 patients; peptichemio, vincristine and prednisone, 13 patients). No difference in response and survival duration was found between p170+ and p170‐ patients. In six of nine patients studied both at diagnosis and following induction chemotherapy the p170+ BMPC% increased irrespective of the type of treatment or outcome.
Verapamil preferentially potentiates in‐vitro cytotoxicity of vincristine on malignant lymphoid cells
Authors: Malik Imtiaz A. , Costea Nicolas V.
Published: February 2007

Verapamil has been shown to overcome acquired drug resistance to vincristine in P388 leukemia both in vitro and in vivo. To study the selectivity of this action, the effect of addition of verapamil on the cytotoxicity of vincristine was studied using lymphocytes from eight patients with chronic lymphocytic leukemia (CLL). lymphoblasts from a T‐acute lymphoblastic leukemia (T‐ALL) cell line (GM 3639), and peripheral blood lymphocytes (PBL) from eight normal healthy volunteers. Using the differential staining cytotoxicity (DiSC) assay, we demonstrated that verapamil at 1 μm concentration potentiated the in‐vitro cytotoxicity of vincristine on CLL and GM 3639 cells in concentrations of 0·04–0·25 μg/l. There was however, no enhancement of cytotoxicity noted against the control PBL. The data demonstrate that verapamil preferentially enhances the in‐vitro cytotoxicity of vincristine on CLL and GM 3639 cells but no enhancement of cytotoxicity is seen against PBL.
Role of blast cell immunophenotyping for the diagnosis and prognosis of acute myeloid leukemia
Authors: Dubosc‐Marchenay Nadine , Lacombe Francis , Dumain Patrice , Marit Gerald , Montastruc Marion , Belloc Francis , Reiffers Josy
Published: February 2007

Bone marrow blast cell antigen expression from 86 patients with de novo acute myeloid leukemias (AML) was studied and correlated with FAB classification and clinical outcome. Among a panel of 14 monoclonal antibodies routinely used for the diagnosis of acute leukemias we studied the expression of six antibodies (CD13, CD15, VIM2, CD33, CD14, CD34) of the granulomonocytic lineage and found that some of them were useful for diagnosis and/or prognosis. For FAB subclassification of AML, the CD13 or VIM2 antigen expression was of no benefit. Monocytic leukemias (M4+M5PD+M5WD) more frequently expressed CD34 antigen (28/31) than granulocytic (M1+M2+M3) subtypes (33/53) (P<0·01). Finally, the most striking differences were found with CD14 antigen expression: CD14 antigen was more frequently expressed in M4+M5 leukemias (21/31) than in M1+M2+M3 subtypes (12/33) (P<0·01). The mean percentage of CD14 positive blast cells was accordingly higher in monocytic leukemias than in granulocytic leukemias and the difference was highly significant (P 0·0001). The CD15 antigen was more frequently expressed in differentiated leukemias (M2+M3+M4+M5WD) (35/44) than in poorly differentiated forms (M1+M5PD) (17/37) (P<0·001). The statistical difference was higher when the mean percentage of CD15 positive blast cells were compared (P<0·0003). Moreover these latter percentages were different in M1 and M2 subtypes (P<0·003). The blast cell expression of CD13, CD14, CD15 or CD33 was not predictive of the length of CR or survival. Moreover, our results support previously published findings suggesting a longer overall survival duration for patients whose leukemic cells do not express the CD34 antigen (P<0·01). We also confirm that patients with the more differentiated subtypes of AML (CD13‐, CD34+) tend to survive longer than patients with the less differentiated subtypes of AML (CD13–, CD34+) (P<0·001).
Protein kinase C isozyme expression in human leukemia–lymphoma cell lines—an immunocytochemical study
Authors: Hojo Hiroshi , Morimura Yutaka , Abe Masafumi , Tominaga Kunihiko , Nozawa Yoshihiro , Nakamura Naoya , Ono Nobutaka , Tasaki Kazuhiro , Yamaguchi Yoshiko , Suzuki Sayuri , Wakasa Haruki
Published: February 2007

There have been an increasing number of reports describing a pivotal role for phosphorylation in cellular responses for cell differentiation and proliferation. We examined an immunocytochemical expression of protein kinase C(PKC) isozymes (type I, II, and III) in 22 leukemia–lymphoma cell lines. Of these cell lines, 21 expressed type II PKC and 17 showed the co‐expression of both types II and III PKC in varying degree. The cell line without PKC activity showed far less [3H]‐TdR uptake and no heterotransplantation in nude mice.

Types II and III PKC appear to relate to cell proliferation in certain leukemia–lymphoma cell lines.
Production of multiple cytokines by Hodgkin's disease derived cell lines
Authors: Klein S. , Jucker M. , Diehl V. , Tesch H.
Published: February 2007

The production of cytokines was analysed in Hodgkin's disease (HD) derived cell lines by enzyme linked immunosorbent tests (ELISA) and Northern blot experiments. Our results demonstrate that HD derived cell lines produce a variety of cytokines, such as ILlα, IL4, IL5, IL6, IL8, TNFα, TNFβ and GM‐CSF but not ILlβ IL2, IL3 and G‐CSF. In cell lines with a high expression of CD25 (the light chain of the IL2 receptor), we found soluble IL2 receptors in the supernatants. In addition, receptors for IL6 could be detected in most of the HD derived cell lines. However the growth of HD derived cell lines, which produce IL6 and IL6 receptors could not be inhibited by anti‐IL6 antibodies. From our data we conclude, that IL6 and additional cytokines may be involved in the biology of HD.
Protein phosphatase 2Aα involvement in granulocytic differentiation of HL‐60 cells
Authors: Sasaki Kazunori , Ikeda Kazuma , Nagai Masami , Shima Hiroshi , Nagao Minako , Takahara Jiro , Irino Shozo
Published: February 2007

Protein phosphatase 2Aα (PP‐2Aα) is one of the catalytic subunits of PP‐2A, which is composed of catalytic and regulatory subunits. In fission yeasts, PP‐2A mutants cause mitotic defects and strikingly different cell cycle phenotypes. In rat hepatocellular carcinomas, mRNA expression of PP‐2Aα was increased compared to that of normal hepatocytes. From these studies, PP‐2Aα has been thought to be involved in proliferation, and we expected that PP‐2Aα would decrease in HL‐60 cells on dimethyl sulfoxide(DMSO)‐induced granulocytic differentiation with decreased growth rate. In this study, we show that PP‐2Aα expression increases in HL‐60 cells on DMSO‐induced granulocytic differentiation, while PP‐1γ, which is one of catalytic subunits of protein phosphatase 1, expression did not change significantly. These results suggest that PP‐2Aα may be involved in regulation of differentiation of hematopoietic cells.
Post‐transcriptional regulation of interferon‐alpha 4 subtype production by lymphoblastoid cells
Authors: Greenway Alison L. , Brandt Evelyn R. , Hertzog Paul J. , Devenish Rodney J. , Linnane Anthony W.
Published: February 2007

The constitutive production of interferon‐alpha (IFN‐α) subtypes by the lymphoblastoid cell lines. Namalwa, Daudi and Raji, was investigated using sensitive and semi‐quantitative flow cytometric techniques. Further, we sought to determine whether the previously described failure of these cell lines to produce IFN‐α‐4 was a result of the deletion of the IFN A4 gene. Cytoplasmic production of IFN‐α‐2 and IFN‐α‐4 was assessed using IFN‐α subtype‐specific antipeptide antibodies and FITC‐labelled secondary antibodies in indirect immunofluoresence‐flow cytometry studies. The constitutive production of IFN‐α‐2 was detected in all three cell lines. Significant increases in fluorescence representing increased production of IFN‐α‐2 and possibly other IFN‐α subtypes were detected after induction by Sendai virus. Approximately 100 per cent of cells in the Namalwa, Daudi and Raji cell populations contained IFN‐α‐2 before and after induction. However, no cells from the same cell populations contained the IFN‐α‐4 subtype. Analysis of genomic DNA isolated from the lymphoblastoid cells using the Polymerase Chain Reaction (PCR) and oligonucleotide primers specific for IFN A2 or IFN A4 confirmed the presence of the genes encoding both IFN‐α subtypes. Furthermore, using reverse transcriptase‐PCR amplification, mRNAs for both IFN‐α‐2 and IFN‐α‐4 were detected. Therefore, in contrast to some leukaemias and derived cell lines where IFN A genes have been deleted, these cell lines of B cell lineage exhibit selective expression of IFN A genes, as a result of altered transcriptional/translational control of IFN‐α expression.
The effect of cytokines on cultured mononuclear cells from patients with B cell chronic lymphocytic leukemia
Authors: Burke Frances , Griffin Dorota , Elwood Nagaire , Davis Carol , Stamp Gordon , Rohatiner Anna , Lister T. Andrew , Balkwill Frances
Published: February 2007

In the past 5 years a number of cytokines have been identified that control B cell development, proliferation, and maturation. The role of such cytokines in the evolution, pathophysiology, and treatment of B cell malignancies is an area of great interest. The in vitro response of freshly isolated peripheral blood mononuclear cells from patients with B cell chronic lymphocytic leukemia (B‐CLL) and a high white cell count, to four cytokines, IFN‐α, IFN‐γ, IL‐2 and TNF, was studied. No culture condition or cytokine resulted in a significant increase in cell number over 4 days, cells survived better in autologous serum than in heat inactivated foetal calf serum, and a small but significant increase in blast cells was seen when the cells were cultured in IL‐2. There was a discrepancy between uptake of thymidine and increase in cell number which can be explained by the low labelling index of these cultures and the fact that cells can incorporate [3H]‐thymidine without going into mitosis. The majority of cultures produced biologically active TNF at levels ranging from 1 to 40 pg/ml. In IFN‐α treated cultures TNF levels were decreased. Cultures contained biologically active IL‐6 at levels ranging from 2 to 2800 U/ml. IL‐6 production was not influenced by other cytokines. Thirteen of 28 patients had detectable IL‐6 in their serum, but in cells lysed no more than 2 h after removal from the patient, message for IL‐6 could not be detected by Northern blotting. Cells also failed to express IL‐1β mRNA but seven of eight patients had low levels of TNF message. Preliminary data using in situ hybridization techniques revealed that whilst no mRNA for IL‐6 was detected, TNF and IL‐1β mRNA were detected in a minoority of mononuclear cells.
Solid tumour with initial presentation in the bone marrow—a clinicopathologic study of 25 adult cases
Authors: Wong K. F. , Chan J. K. C. , Ma S. K.
Published: February 2007

This study reviews the clinicopathologic features of 25 adult patients without a known history of malignancy presenting with metastic carcinoma in the bone marrow. The disease mainly affected middle‐aged to elderly males (mean age, 61·6 years). Bone pain, generlized or confined to the back, was a common presenting complaint. Organomegaly was often absent. Laboratory abnormalities included anaemia, leukocytosis, thrombocytopenia and a leukoerythroblastic blood picture. Serum alkaline phosphatase level was raised in the majority of cases. In about one‐third of the cases, malignancy was not suspected clinically, and bone marrow aspiration was carried out because of incidental finding of abnormal blood counts. The marrow aspirate findings were characterized by numerous to sparse cohesive tumour clusters with nuclear moulding. Over two‐thirds of the patients had metastatic adenocarcinoma, and the lung was found to be the commonest site of primary disease. We conclude that since the marrow infiltration can be subtle, marrow smears should be carefully scrutinized for tumour cells in patients with leukoerythroblastic blood picture, in particular those with an elevated serum alkaline phosphatase level.
Copp chemotherapy for elderly patients with intermediate and high grade non‐Hodgkin's lymphoma
Authors: Liang Raymond , Todd David , Chan T. K. , Chiu Edmond , Lie Albert , Ho Faith
Published: February 2007

One hundred and forty‐one consecutive patients above and 231 below the age of 60 years with previously untreated intermediate or high grade non‐Hodgkin's lymphoma were included in this study. Patients above the age of 60 years were treated with the COPP chemotherapy regimen. The younger patients, at or below the age of 60, received a doxorubicin‐containing regimen (119 had CHOP, 65 had BACOP and 47 had m‐BACOD). For stage I patients, the clinical results were similar but for stage II, III or IV disease, those receiving COPP had significantly worse CR rate and survival than those who had a doxorubicin‐containing regimen. Multivariate analysis on patients receiving the COPP chemotherapy revealed that the independent prognostic variables significantly determining CR rate and survival included clinical stage (p =0·04) and serum lactate dehydrogenase level (p =0·001). Myelosuppression was the major toxicity following COPP chemotherapy in this group of patients. There were 10 (7 per cent) treatment‐related deaths. Compared to the reported results using doxorubicin‐containing regimens to treat elderly patients with aggressive NHL in the literature, the more aggressive treatment does not appear to improve significantly the clinical outcome of this group of patients and seems to produce treatment results very much similar to COPP. However, accurate comparison is difficult because of the variation in the patient characteristics. Further prospective controlled randomized trials will be necessary to determine the optimal therapy for these patients.
Subcutaneous low dose arabinosyl‐cytosine and oral idarubicin in high risk adult acute myelogenous leukemia
Authors: Kusnierz‐Glaz C. R. , Normann D. , Weinberg R. , Fuchs R. , Flasshove M. , Hiddemann W. , van de Loo J. , Büchner Th.
Published: February 2007

In order to further explore low dose chemotherapy for high risk acute myelogeneous leukemia (AML), low dose Ara‐C and oral idarubicin (LAI) were given to 33 patients of 24–84 (median 66) years with AML after myelodysplastic syndrome (MDS) (12 patients), refractory AML (13 patients), and AML with contraindications to intensive chemotherapy (8 patients). Patients received 1 to 4 cycles of Ara‐C 10 mg/m2 q 12 h s.c. inject. on days 1–14 and idarubicin 20 mg/m2/d orally days 3, 4, 5. Three patients attained complete remission, four patients partial remission and one patient minor response, whereas 11 patients succumbed to early mortality from hemorrhage (two patients) and/or infections (10 patients). Three of 13 patients with heavily pretreated refractory AML went into remission compared to 3/12 with AML after MDS and 1/8 with AML and contraindications against intensive treatment. Median duration of CR is 102 (70–488+) days. Thirty‐two of 33 patients developed grade 4 hematological toxicity requiring platelet transfusions. The non‐hematologic toxicity was acceptable. LAI provides a standardized therapeutic option especially for heavily pretreated patients with AML.
Acute lymphocytic leukemia (all) in elderly patients
Authors: Virgilio J. F. , Moscinski L. C. , Ballester O. F. , Corrado C. , Guida C. , Balducci L. , Saba H.
Published: February 2007

Objective: To compare the clinical and biologic characteristics, response to therapy and outcome of adult patients with ALL above and below the age of 55.

Design: Retrospective review of clinical and laboratory data.

Setting: University affiliated Cancer Center and Veteran's Hospital.

Patients: Thirty‐three newly diagnosed, consecutive, adults with ALL seen over a nine‐year period.

Results: while no differences were demonstrated in the distribution of recognized prognostic indicators (such as cytogenetic abnormalities or immunophenotype), individuals over the age of 55 had significantly lower remission rates and shorter survivals.

Conclusions: The outcome of elderly patients with ALL is very poor. This is primarily related to an increase in the number of early deaths during induction, as well as a higher prevalence of disease refractory to standard chemotherapy programmes. There is a need for new treatment protocols designed for the elderly ALL patient, as well as a better understanding of the unique biological characteristics of the disease in this age group.
Epstein‐barr virus‐related lymphomagenesis in a child with wiskott‐aldrich syndrome
Authors: Gulley Margaret L. , Chen Chi‐Long , Raab‐Traub Nancy
Published: February 2007

Epstein‐Barr virus (EBV) DNA was detected in immunoblastic lymphoma arising in a child with the primary immunodeficiency, Wiskott‐Aldrich syndrome. Southern blot analysis of the structure of the EBV genome revealed that the lymphoma was monoclonal and contained episomal EBV DNA. The EBV latent genes, latent membrane protein 1 (LMP1) and the EBV nuclear antigen 2 (EBNA2), were detected by immunohistochemistry in the Wiskott‐Aldrich lymphoma but not in an EBV‐positive Burkitt's lymphoma, implying that host immune factors could influence EBV gene expression. Hybridization in situ demonstrated expression of EBV‐encoded RNA (EBER), the cellular c‐fgr protooncogene, and CD23 B‐cell activation transcripts in the Wiskott‐Aldrich lymphoma whereas EBER and c‐fgr but not CD23 were expressed in the Burkitt's lymphoma. These data suggest that in primary immunodeficiency‐related lymphoma, LMP1 and EBNA2 are expressed and that this expression correlates with expression of CD23. This supports previous in vitro studies showing that CD23 is specifically induced by LMP1 or EBNA2 genes. In contrast, expression of c‐fgr may be independent of expression of these EBV latent genes.
Reinforced HEAV'D therapy for adult acute lymphoblastic leukemia: Improved results and revised prognostic criteria
Authors: Bassan Renato , Battista Raffaele , Montaldi Anna , Rambaldi Alessandro , D'emilio Anna , Viero Piera , Borleri Gianmaria , Buelli Maurizio , Dini Enrico , Barbui Tiziano
Published: February 2007

Thirty‐six adults with acute lymphoblastic leukemia (ALL) were treated with adriamycin, vincristine. prednisolone, and asparaginase for remission induction, followed by vincristine‐adriamycin‐cyclophosphamide consolidation courses, cranial irradiation, a short ara‐C plus VM‐26 pulse, and vincristine plus cyclophosphamide rotating weekly with ara‐C plus VM‐26 for three months (reinforced HEAV'D). Thirty‐one patients achieved a complete remission (86 per cent). Compared with historical results from a prior study, age >30 years, absolute blast count >15 × 109/1, and CD10‐negative immunophenotype were not associated with higher relapse rate and shorter survival, suggesting a positive effect from intensification therapy with ara‐C and VM‐26 in these poor prognostic categories. However, patients with an abnormal karyotypic pattern or a positive molecular study for BCR‐ABL rearrangement detecting t(9;22) had a far greater likelihood of treatment failure (probability of remission at 3 years 0·10) than those with normal karyotype or negative molecular study (probability 0·70), and those not studied or with insufficient methaphases (probability 0·50) (p<0·05 by log‐rank test). These results underline the prognostic importance of chromosomal abnormalities and the usefulness of ara‐C and VM‐26 in the management of adult ALL.