bluuebunny/crossref_metadata_2025_split huggingface dataset:
Five Years Update Results of Basiliximab (BAMAB) Therapy for Acute Refractory Graft Versus Host Disease (AGVHD).
Authors: Funke Vaneuza A.M. , Bonfim Carmem M. , Bitencourt Marco A. , Setubal Daniela C. , Ruiz Jefferson , Medeiros Carlos R. , Neto Jose Z. , Pasquini Ricardo 
Published: April 2020

Abstract
The IL-2 activation of RAS pathway promotes lymphocyte proliferation, differentiation and development of A-GVHD. This mechanism can be inhibited by basiliximab, a chimeric murin-human monoclonal antibody which binds to the alpha chain of interleukin-2 receptors on activated T-cells. Basiliximab is already largely used to prevent acute rejection after renal transplantation, but the experience with this drug on BMT setting is still limited. We treated 34 patients (pts) with severe refractory A-GVHD with Basiliximab from december 1998 to october, 2003. Median age was 13 years (range: 2 to 38). Most of the patiens had received an unrelated BMT (73%). Cell source was bone marrow in 88% and cord blood in 12% of the patients. Diagnosis included acute leukemia (9 pts), MDS (4 pts), CML(9 pts), Fanconi anemia (9 pts), and SAA (3 pts). Because of a half life of about 7 days, BAMAB schedule was 40mg weekly for 2–3 doses (adults) and 20 weekly for 2–3 doses (children). All pts had a-GVHD grade III-IV, manifesting from day 6–248 after transplant (M: 24 d), while on cyclosporin, and refractory to association with steroids (2–5mg/kg/d). Skin was involved in 32, GI in 25 and liver in 23 patients. Median follow-up was 196 (range: 35–1847) days. Overall response rate was 82% (CR: 11 pts, PR: 17 pts). Two pts (8 %) were not evaluated due to early death. Response varied according to the site involved, being complete in 84% of skin, 48% of GI and 26% of liver GVHD. Duration of response varied from 5–1103 d (M: 38 d). There were no infusion-related reactions. Eleven pts are alive (32%), 7 pts with complete response, 3 with partial response and 1 pt without response. Acute GVHD reactivation was seen on 41% of the patients, but half of them could be rescued with other therapies (MMF, PUVA, steroids). Infection was the main cause of death, being responsible for 83% of all deaths (disseminated CMV-4 pts, fungal infection-6 pts and sepsis-8 pts). Other causes of death included bleeding (2pts) and relapse (2 pts). In conclusion, basiliximab was able to induce response on patients with refractory A-GVHD. Prospective studies with this drug are necessary to address the optimal dose, schedule and incidence of infection.
Comparison of Empiric Versus Prophylactic Administration of Ceftazidime during Neutropenia Associated with Reduced-Intensity Allogeneic Stem Cell Transplantation (RIST).
Authors: Donley Kyle M. , Gea-Banacloche Juan C. , Dean Robert M. , Steinberg Seth M. , Childs Richard W. , Odom Jeanne , Castro Kathleen , Chinn Tracey , Fowler Daniel H. , Bishop Michael R. 
Published: April 2020

Abstract
Broad spectrum antibiotics are sometimes used prophylactically during the neutropenic phase of stem cell transplantation, but this practice is controversial. Possible benefits include the prevention of fever and infectious episodes. Possible disadvantages include increased usage of antibiotics with associated increases in cost, toxicities and development of antibiotic resistance.
OBJECTIVE: To compare prophylactic (PRO) administration of ceftazidime at the beginning of neutropenia (ANC &lt;500) vs. empirical (EMP) initiation of ceftazidime for neutropenic fever in RIST patients during the pre-engraftment period.
METHODS: Retrospective analysis of all patients who received a RIST for hematologic malignancies in two different bone marrow transplant units at the NIH Clinical Center between 2000 and 2003. The PRO group was composed of 41 patients who received prophylactic ceftazidime 2 g iv q 8h when ANC &lt;500. The EMP group was composed of 40 patients who received ceftazidime during neutropenia only if fever developed. Both groups were comparable in terms of baseline disease, age, sex, conditioning regimen (FLU/CY) and gut decontamination. Mean duration of neutropenia was 10.8 days in the PRO group and 13.7 days in the EMP group (p &lt; 0.05), due to differences in GVHD prophylaxis and GCSF usage.
RESULTS: The PRO group presented less episodes of neutropenic fever (16/41, 39% vs. 27/40, 67.5%, p &lt; 0.05), less microbiologically documented infections (4/41, 10% vs 17/40, 43% p &lt; 0.05) and less episodes of bacteremia (1 vs. 7). By Kaplan-Meier analysis the median time to developing fever was significantly longer in the PRO group (9.6 vs 6.8 days p = 0.03). The PRO group received, on average, 5.5 less days of broad-spectrum antibiotics (11.8 vs 17.3). The average number of days on ceftazidime was 10 in the PRO group and 7 in the EMP group. There were no significant toxicities associated with antibiotic use. The susceptibility to ceftazidime on the bacterial isolates from both transplant units did not change significantly between 1999 and 2003, despite the different patterns of antibiotic use.
CONCLUSION: Prophylaxis with ceftazidime may prevent neutropenic fever and microbiologically documented infections during the pre-engraftment phase of RIST, and may result in decreased utilization of broad-spectrum antibiotics.
Reduced Intensity Conditioning Regimen for Allografting Following Cytoreductive Autografting in Metastatic Breast Cancer.
Authors: Carella A.M. , Beltrami Germana , Corsetti Maria T. , Scalzulli Potito , Carella Michele , Gonella Roberta , Ballestreo Alberto , Patrone Franco 
Published: April 2020

Abstract
We postulated that it is possible to safely extend the benefits of allografting to metastatic breast cancer by combining cytoreduction achieved with high-dose therapy and autologous stem cell transplant (HDT/ASCT) and graft versus tumor effect mediated through transplanted donor immune cells with nonmyeloablative allografting (RICT). Seventeen patients, 41 years of age (range, 31–57), with heavily pretreated disease were given HDT/ASCT. No patient died after HDT/ASCT. Thirty-one to 92 days (median, 51 days) after HDT/ASCT the patients received fludarabine 30 mg/m2/day x 3 days and cyclophosphamide 300 mg/m2/day x 3 days and donor PBPC from HLA-identical siblings. Postgrafting immunosuppression consisted of cyclosporine and methotrexate. Donor lymphocyte infusions were given to 11 patients with stable mixed chimerism and/or progressive disease, who did not show signs of GVHD. Thirteen patients (76%) achieved sustained donor engraftment. Three patients achieved partial remission (PR) after HDT/ASCT and complete remission (CR) after RICT; another no-responsive patient achieved PR for an overall response rate of 4/17 (22%). The first signs of responsiveness in CR patients began at day +80, +90 and +110 and the maximal response was achieved on day +240, +300 and +390. The 3 remitters patients achieved full chimerism and developed GVHD before regression of the disease. Grade ≥II aGVHD occurred in 5 patients (29%) and extensive cGVHD in 5 patients (29%). No transplant-related deaths (TRD) were observed during the first 100 days. Three patients died of extensive cGVHD in the first year. At April 2004, 5/17 patients (29%) are alive 90–2160 days (median, 1320) from RICT. In conclusion, this 2-step approach is a feasible procedure in metastatic breast cancer patients; the exploitation of graft versus tumor effect is a promising finding.
Allogeneic Transplantation for Adult Acute Lymphoblastic Leukemia (ALL) with Rituximab or Campath I-H.
Authors: Khouri Issa F. , Saliba Rima M. , Kebriaei Partow , Ma Carrie , Ippoliti Cindy , Couriel Daniel R. , de Lima Marcus , Giralt Sergio , Qazilbash Muzaffar H. , Gajewski James L. , Champlin Richard E. 
Published: April 2020

Abstract
Because of potential synergy with chemotherapy and non-overlapping toxicity, we investigated the addition of Rituximab or Campath 1-H to the standard myeloablative conditioning regimen of cyclophosphamide (60 mg/kg daily x 2) and total body irradiation (12.0 Gy in four fractions) prior to allogeneic transplantation for ALL. Transplantation was performed on day 0. Rituximab was added if patients’ disease expressed CD20+ &gt; 20% by flow-cytometry. It was administered (375 mg/m2 ) on days −6, −1, +7 and +14. Campath I-H (10 mg daily intravenously, days −6 to −2) was added if patients’ CD20 expression was &lt;20% and CD52 &gt;20%. Thirty-two adult consecutive patients were studied. Eleven were in first remission with poor prognostic features, 11 in 2nd remission, and 10 were ≥ 3rd remission, or in relapse. Twenty-nine patients had B-cell, two had T-cell and one had an undifferentiated phenotyping. The study group included 19 males and 13 females of median age 35 yrs (range, 19–57). Median # of prior chemoregimens received was 2 (range, 1–6). In both groups of patients, prophylaxis for GVHD consisted of a combination of tacrolimus and methotrexate. Pharmacokinetic studies in patients who received Campath I-H showed no detectable level of the antibody one-day prior to- or after the infusion of the donor graft. Median follow-up for survivors was 19 months. Outcomes were:
Campath-study group Rituximab-study group P -value Prior Chemoregimens (range) 2(1–6) 2(1–3) 0.04 Donor Type     Matched unrelated 3(28%) 8(38%) 0.2     Matched sibling 7(63%) 12(57%)     Mismatched sibling 1(9%) 1(5%) Cell Source     PB 8(73%) 11(52%) 0.2     Marrow 3(27%) 10(48%) Disease Status     CR1/CR2 5(45%) 17(81%) 0.05     Others 6(55%) 4(19%) Median time ANC &gt;500 13 12 0.07     (range) (11–17) (10–24) Median time Platelets &gt;20K 13 13 0.8     (range) (6 – 31) (7 – 34) Day 100 TRM 0 1(5%) Acute GVHD II–IV (N,% kM) 2 (18%) 5 (24%) 0.7 Acute GVHD III–IV (N, % kM) 0 2 (9%) Chronic extensive GVHD (N, cumulative incidence) 3 (27%) 9 (54%) 0.4 Overall Survival (18 mos) (95% CI) 53% (21 – 77) 52% (26 – 73) 0.9 Disease-free survival (18 mos) (95% CI) 54% (23 – 75) 37% (15 – 60) 0.8
No prognostic factor was found to be of significance for survival, disease-free survival, or relapse. This included: age (&lt;35 vs ≥ 35), source of graft, disease status at transplant, # prior regimens (&lt;2 vs ≥ 2), acute or chronic GVHD, use of Rituximab or Campath. Our results indicate that the addition of Rituximab or Campath I-H in allogeneic transplantation for ALL is safe. There was no delay in engraftment and no added toxicity or risk of mortality. Longer follow-up is needed to evaluate the impact of this strategy upon survival and relapse.
Clinical Status Longer than One Year Post-Transplantation in 4 Recipients of Non-T-Cell-Depleted HLA-Haploidentical Transplantation Based on Feto-Maternal Microchimerism.
Authors: Yoshihara Takao , Morimoto Akira , Kuroda Hiroshi , Ishida Hiroyuki , Imamura Toshihiko , Maruya Etsuko , Saji Hiroh , Imashuku Shinsaku 
Published: April 2020

Abstract
The long-term presence of fetal hematopoietic cells in the maternal blood after childbirth indicates maternal tolerance to fetal inherited paternal antigens (IPA), and also that of maternal hematopoietic cells in the offspring’s blood after birth indicates mutual tolerance to non-inherited maternal antigens (NIMA) among sibling. Based on such recent feto-maternal microchimerism / tolerance theory, more than 40 cases have received non-T-cell-depleted (non-TCD) HLA-haploidentical stem cell transplantation (SCT) for various hematological malignancies in Japan. Their early post-SCT clinical courses have been reported; however, long-term outcome and quality of life of such SCT recipients are largely unknown. In our hospitals, we used non-TCD cells from haploidentical family donors for transplantation in 5 children with hematologic malignancies. Among those children, four have been alive for more than one year. Three of the 4 recipients still require prophylactic immunosuppressants for chronic GVHD. Only one case developed chronic GVHD (skin limited). Various late complications are noted in 3. Three children showed complete school attendance. Two of the three are also allowed to participate in physical exercises. These results suggest that quality of life in long-term survivors in childhood from non-TCD HLA-haploidentical SCT based on feto-maternal microchimerism seems acceptable although the numbers are still small and the follow-up period is short.
Patients characteristics
Case Age Diagnosis Status Donor HLA mismatch acute GVHD Survival after SCT (days) 1 6 ALL CR1 (advanced remission) NIMA-mismatched sibling 2 2 CR, 802+ 2 11 ALL Rejection after UCBT (CR2) Mother 2 1 CR, 775+ 3 16 MLL Refractory relapse after UCBT Mother 2 1 CR, 519+ 4 14 CML Blastic phase Mother 2 1 CR, 473+ 5 6 ALL Rejection after UCBT (Rel 1) Mother 3 2 Dead, 93
Present status of long-term survivors
Case chronic GVHD Karnofsky score Late complications School attendance Physical exercise Medication 1 - 100 - complete permitted - 2 - 100 hypothyroidism complete permitted FK506 3 + (skin) 70 diabetes, esophageal stricture no prohibited PSL+MTX, insulin 4 - 100 arrhythmia complete prohibited FK506
Double-Unit Cord Blood Transplantation in Japan.
Authors: Kai Shunro , Misawa Mahito , Iseki Tohru , Takahashi Satoshi , Kishi Kenji , Hiraoka Akira , Kato Shunnichi , Hara Hiroshi 
Published: April 2020

Abstract
Cord blood (CB) is being increasingly used as a source of hematopoietic stem cells for patients in need of stem cell transplantation when a HLA matched-related or unrelated donor is not found. However, cord blood transplantation (CBT) in adults is limited by its lower cell dose. We have started investigating whether transplant with two units of CB will make an engraftment faster and improve outcomes in adult patient lacking a suitable single CB unit. Four transplant centers have participated in this clinical study. Eligibility for this study are as follows; 1) high-risk or advanced hematological malignancy without a related donor, 2) no HLA-matched unrelated BM donor in JMDP or requirement for urgent transplantation, and 3) absence of single HLA 0–2 antigen-mismatched cord blood unit with a cell dose of &gt;2.5x10e7/kg. Eleven patients with hematological malignancies (AML 7, MLL 2, ALL 1, LBL 1) were transplanted with two CB units, following myeloablative conditioning with fractionated TBI(12Gy)+ G-CSF (5?g/kg/dx2days) combined ara-C (12g/?) +CY (120mg/kg) or TBI(12Gy) + CY (120mg/kg). GVHD prophylaxis consisted of short term MTX and CSA. The median age was 33 years (range; 19–52) and median weight was 68kg (range 48– 84). CB grafts were HLA 0–2 antigen-mismatched to the patients and each other, with a median total cryopreserved cell dose of 3.88x10e7/kg (range; 2.83–4.79) and median CD34+ cell dose of 1.06x10e5/kg (0.62–2.6). Nine out of 11 patients engrafted successfully, and had 96–100% single donor chimerism at day+28 bone marrow aspirate. The median time to neutrophil engraftment (ANC &gt;500 /?) was 21days (16–26) and median time to platelets &gt;50000 /?was 53 days (32–98). Nine patients who survived more than 28 days had AGVHD (grade I in 2, II in 3, III in 1), and CGVHD (limited type) was developed in 4 of the 6 evaluable patients. Two patients died of sepsis at day 7 and 27 and one had relapse at day 249. Nine patients are now alive 3 to 16 months after CBT. These preliminary results suggest that multiple unit CBT seems to be useful for adult with hematological malignancies lacking an appropriate BM donor or a single CB unit. Further studies with double-unit CBT may be warranted.
Comparison of the Feasibility of Adult Allogeneic Umbilical Cord Blood Transplantation between the Myeloablative Conditioning Regimen and the Non Myeloablative One.
Authors: Tashiro Haruko , Kozai Yasuji , Noguchi Mitsuho , Goto Moritaka , Kawasugi Kazuo , Kodo Hideki , Shirafuji Naoki 
Published: April 2020

Abstract
Aim: To make clear the feasibility of non-myeloablative conditioning on the adult allogeneic umbilical cord blood transplantation, we compared the result between patients receiving the myeloablative (conventional) transplantation (CT) and the reduced intensity stem cell transplantation (RIST) in point of the engraftment, and the incidence of GVHD. Patients’
characteristics and Methods: Patients were admitted to our hospitals to receive umbilical cord blood transplantation during May 1999 to May 2004. CT group (n=23): Median age was 33 years. Diagnoses were included AML (n=9), ALL(n=7), NHL(n=4), MDS(n=2), CML(n=1). Preparative conditioning regimens were; TBI/Ara-C/CY (n=16), TBI/VP-16/CY (n=4), TBI/CY (n=3). GVHD prophylaxis was; Cyclosporine A (CsA) (n=11), CsA with short term Methotrexate (MTX) (n=10), Tacrolimus with short term MTX (n=2). The transplanted median cell number was 2.40 x 10^7/kg. HLA disparities were; 1AMM (n=5), 2AMM (n=18), 3AMM (n=3). RIST group (n=13): Median age was 54 years. Diagnoses were; AML (n=3), NHL (n=5), HD (n=2), ATL (n=1), CLL (n=1), CMMoL(n=1). Preparative conditioning regimens were; Flu/ L-PAM (n=4), TBI/ Flu/ L-PAM (n=1), TBI/ Flu/ CY (n=3), TBI/ Flu (n=1), TBI/ Flu/ BU (n=4). GVHD prophylaxis was; CsA (n=5), CsA with MMF (n=7), Tacrolimus (n=1). The transplanted median cell number was 2.49 x 10^7/kg. HLA disparities were; identical (n=3), 1AMM (n=2), 2AMM (n=6), 3AMM (n=2).
Result: The rate of engraftment failure including conditioning failure, and autologous recovery was 14.8 %in CT and 38.1%in RIST, respectively. The median duration of the engraftment of neutrophils in CT and RIST were 24 days and 19 days, respectively. Patients with Grade II-IV acute GVHD were 15 (65.2%) in CT and 8 (61.5%) in RIST, respectively. The incidence of Grade III-IVacute GvHD was 7 ( 30.4%) and 5(38.4%), respectively.
Conclusion: Engraftment in RIST was achieved earlier than CT, however the incidence of engraftment failure was increased in RIST. There were no significant differences on the incidence of acute GVHD between two groups. Further observations, especially long-term disease-free survival are seemed to be very interesting to ascertain RIST on adult umbilical cord blood transplantation.
Reduced Intensity Allografts for Acute Myeloid Leukemia: Defining the Role of Conditioning and Donor Alloreactivity.
Authors: Devine Steven M. , Hallemeier Chris , Fenske Timothy , Vij Ravi , DiPersio John F. , Adkins Douglas A. 
Published: April 2020

Abstract
The role of reduced intensity allografting in the treatment of patients with acute myeloid leukemia (AML) is unclear. While more patients may survive the initial period following allografting in comparison to those receiving full intensity transplants, the risk of relapse may be greater, particularly in patients not in remission at the time of transplantation. Here we report the results of allogeneic transplants using either cytokine mobilized peripheral blood (PB) or bone marrow (BM) following a reduced intensity conditioning (RIC) regimen. 131 patients with AML were all conditioned with an identical regimen containing Cyclophosphamide at 120mg/kg iv over 2 days (days −3 and −2) followed by a single dose of total body irradiation at 550cGy on day −1. HLA-identical (HLA-ID) siblings donated cytokine mobilized PB to 62 recipients and unrelated donor (UD) BM was used for 69 patients. GVHD prophylaxis consisted of single agent cyclosporine (CSP) for recipients of HLA-ID allografts and CSP, methotrexate, and methylprednisolone in recipients of UD BM. The median age of recipients was 45 years (range 21–70), with 55 males and 76 females. 43 pts were in CR1, 33 in CR2, and 55 had relapsed (rel) or refractory (ref) disease. 59 of 69 recipients of UD BM were serologically identical with their donors at 6/6 antigens. There were no graft failures in either group.With a median follow-up of over 18 months, the results of transplantation are presented in the Table.
Results of Transplantation
Clinical Outcome Allograft Source HLA-ID PB UD BM Grade 2–4 Acute GVHD 42% 51% Extensive Chronic GVHD 57% 61% Disease free survival (DFS) at 2 years CR1 49+/−10% 39+/−12% CR2 19%+/−12% 38+/−11% Rel/Ref 17+/−8% 0%
For pts transplanted in CR1, the results are comparable to those observed following fully ablative conditioning, particularly since many pts were transplanted due to high risk karyotype. In CR2, outcomes following RIC were superior in recipients of UD BM compared to HLA-ID PB, possibly due to a greater graft versus leukemia effect. UD BM was ineffective in pts with rel/ref AML. Of interest, the 2 year DFS in pts with rel/ref AML following receipt of HLA-ID PB was 17% overall, but was 28% in those that developed any acute GVHD versus 0% in those that did not (P&lt;0.02). In conclusion, while the role of RIC in the treatment of pts with AML requires further clarification, our findings suggest that in pts beyond CR1, clinical evidence of donor alloreactivity appears to be critical for ensuring durable DFS.
Single Institution Experience with Two High-Dose Chemotherapy (HDC) Conditioning Regimens Prior to Autologous Stem Cell Transplant (ASCT) for Multiple Myeloma (MM).
Authors: Benson Don M. , Elder Patrick J. , Lin Thomas , Blum William , Penza Sam , Avalos Belinda , Byrd John C. , Copelan Edward , Farag Sherif S. 
Published: April 2020

Abstract
HDC with ASCT has become a standard treatment for patients with MM. Based on the results of recent trials, the use of melphalan (MEL) 200mg/m2 has emerged as the preferred HDC conditioning regimen, although research towards defining the optimal preparative regimen for these patients continues. We report our institution’s experience with two sequential patient cohorts receiving HDC regimens prior to ASCT as treatment for MM. From July 1992 through August 2003, 62 patients received the combination of high-dose busulfan (1 mg/kg orally every 6 hours for 14 doses on day −8 to −5), etoposide (60 mg/kg 36-hour continuous intravenous [IV] infusion on days −5 and −4) and cyclophosphamide (60 mg/kg/day IV on days −3 and −2) (BVC), and 48 patients received MEL 200 mg/m2 as a single IV dose on day −2). Prior to conditioning, peripheral blood stem cells were mobilized with etoposide or cyclophosphamide followed by filgrastim (gCSF) given subcutaneously at 10 μg/kg/day. At least 5 x 106 CD34+/kg ideal body weight was targeted for collection. Two patients in the BVC group had CD34+ cells harvested directly from bone marrow. In both groups, autologous stem cells were infused on day 0. Patients received aggressive supportive care measures including intravenous anti-emesis medications and analgesia as required, prophylactic antibiotics, blood product transfusion and filgrastim (gCSF) support. Patients treated with BVC and MEL were similar in age (median ages, 55 vs 58 years), MM subtype (IgG in BVC = 65%, IgG in MEL = 56%) and timing of transplant from diagnosis. Median time from diagnosis to transplant for BVC was 289 days (d), and for MEL was 287 d. 90% of BVC patients and 91% of MEL patients were receiving HDC/ASCT as second-line therapy. Whereas 39% of BVC patients and 58% of MEL patients had stage III disease, 30% of BVC patients and 23% of MEL patients were classified as having “progressive” or “refractory” disease at time of transplant. Median beta-2 microglobulin for BVC patients was 2.99 mg/dl and for MEL patients was 3.87 md/dl. Patients were similar in median length of hospitalization (BVC = 20 d vs MEL = 16 d), median duration of neutropenia (BVC = 9 d vs MEL = 10 d), and mdian duration of thrombocytopenia (BVC= 15 d vs MEL = 17 d). Toxicities of therapy were similar between groups, although there were two treatment related mortalities (TRM) in the BVC group (one attributed to infection, one to hepatic veno-occlusive disease). The median progression-free survival was similar between groups (BVC = 803 d vs MEL = 749 d, p &gt; .05). The median overall survival (OS) for BVC pts was 1394 d while the median OS for MEL pts has not been reached to date (p&gt;0.05). Our results indicate that MEL and BVC achieve similar long-term outcomes in patients with MM.