Matched Unrelated Donor Stem Cell Transplantation for Patients with Diffuse Large Cell B Cell Lymphoma: A Retrospective Analysis of 118 Patients Registered through the European Group for Blood and Marrow Transplantation (EBMT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 602-602 ◽  
Author(s):  
Irit Avivi ◽  
Carme Canals ◽  
Goli Taghipour ◽  
Dietger Niederwieser ◽  
Lothar Kanz ◽  
...  

Abstract Matched unrelated donor stem cell transplantation (MUD-SCT) may provide a treatment option for patients with diffuse large B cell lymphoma (DLBC) who have failed other conventional therapies and do not have a compatible sibling donor available. We present data of 118 DLBC patients, 69 males and 49 females, aged 18 to 66 years (median 43 years), treated with a MUD-SCT between January 1997 and July 2005 and reported to the EBMT registry. Median time from diagnosis to MUD-SCT was 25 months (range, 3 – 205), and 64% of the cases had failed a previous autologous transplant (ASCT). At allogeneic transplantation, 25% of the patients had chemorefractory disease. Peripheral blood was the source of hematopoietic stem cells in 70% of the cases and reduced intensity conditioning regimens (RIC) were used in 52% of the cases. After a median follow up of 26 months, the estimated 2-year non-relapse mortality (NRM), relapse rate (RR), progression free survival (PFS) and overall survival (OS) for the whole series were 29%, 35%, 36% and 43%, respectively. Grade II–IV acute graft-versus-host-disease developed in 32% of patients. Patients selected for RIC protocols were older (median age of 44 years vs 38 years, p = 0.02) and more heavily pre-treated; 75% had failed a previous autograft compared with 53% in the conventionally treated group (CC) (p = 0.01). Despite these unfavorable factors, the 2-yr NRM for RIC patients was significantly lower than in CC patients: 19% vs 39% (p = 0.03). Unfortunately, this advantage was offset by an increased RR in this group of patients (2-yr RR: 46% vs 24%, p = 0.2), resulting in a very similar PFS and OS for both types of conditioning regimens. The prognostic factor with highest impact on PFS was refractory disease at transplantation (RR = 1.8; 95%CI 1.1 −3.1, p = 0.02). The 2-year PFS for patients transplanted with sensitive disease was 40% irrespective of the conditioning regimen used. In sensitive patients undergoing a RIC transplant, the NRM was significantly lower with respect to CC regimen (14% vs 38%, p = 0.02), resulting in an improved PFS and OS (41% vs 37% and 50% vs 46% respectively). PFS in patients transplanted with refractory disease was generally poor (25% at 2 years). However, CC seemed to provide a better outcome than RIC (2-yr PFS of 35% vs 16%). In conclusion, MUD-SCT constitutes a treatment option for patients with DLBCL failing other conventional treatments, particularly for those patients being allografted in sensitive disease. The high RR observed with reduced intensity protocols does not allow to demonstrate a clear long-term benefit of this approach in this setting.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5488-5488 ◽  
Author(s):  
Albrecht Reichle ◽  
Ernst Holler ◽  
Anna Berand ◽  
Reinhard Andreesen

Abstract Feasibility and high efficacy of repetitive dose-intensive chemo-immuno-therapy in relapsed and refractory aggressive B-cell lymphoma (adjusted IPI at relapse 2 and 3) was proven by double-induction followed by tandem high-dose chemo-immuno-therapy with stem cell transplantation including a treosulfan-based conditioning regimen. For cytoreduction and stem cell mobilisation, 2 cycles of a cisplatin-based chemotherapy plus rituximab (R), R-VIPE or R-DHAP, were applied followed by two identical cycles of high-dose chemotherapy (HD-CT) consisting of treosulfan 14 g/m2 iv day −4 to day -2, carboplatin 300 mg/m2 iv day −4 to day −2 and etoposide 500 mg/m2 iv day −2 to day −4. Each HD-CT was combined with rituximab 375 mg/m2. Thirty patients (pts), mean age 53 years (range 35–68), stage III: n=9, stage IV: n=21, have been enrolled. 80% of the pts suffered from early relapse within 6 months (n=6) or refractory disease and no available matched related or unrelated donor (n=18), 6 pts had a late relapse (≥ 6 months). All patients received previously CHOP-based CTs. Histology revealed diffuse-large cell lymphoma (n=19), follicular lymphoma Grade 3 (n=6), immunoblastic lymphoma (n=3), and mantle cell lymphoma (n=2). In 7 pts both, low- and high-grade lymphomas were observed. Only one stem cell mobilization was necessary to collect sufficient CD34+ cells for two transplantations. Median hematologic recovery (> 1.0 leukocytes/nl and platelets >20/nl) after 1st and 2nd HD-CT was achieved by day 10 (8–11). No therapy-related death occurred. CTC °III and °IV non-hematologic toxicities were as follows: 11 of 29 pts after 1st HD-CT had °III toxicities (infection, vomiting, enteritis, stomatitis, diarrhea), after 2nd HD-CT 10 of 27 pts, respectively. Complete remission (CR 3 months post transplantation) was achieved in 22 of 30 pts (73%). CR was documented after double-induction (n=2), 1st HD-CT (n=9), and 2nd HD-CT (n=11), PR in 6 pts, and 2 pts had progressive disease during induction CT and HD-CT, respectively. At a median observation time of 19 months (range 3.6 to 4.6 months) 26 pts (87%) are alive. Sequential R-HD-CT results (in poor risk pts) in a median PFS of 14.0 months (CI 8.7 to 19.3 months), median overall survival (OS, intent-to-treat analysis) has not been reached (at 4 years 72%). In conclusion, treosulfan-based tandem R-HD-CT is feasible with a manageable toxicity profile. CR and continuous CR rates argue for a dose-response relationship even in high-risk patients with aggressive B-cell lymphomas. Some poor risk pts seem to be cured with the treosulfan-based HD-chemo-immuno-therapy. In cases of progression rescue therapies may be successfully administered as shown by the favorable OS rate. This study has now been extended as a multicenter trial.


2021 ◽  
Vol 12 ◽  
pp. 204062072110637
Author(s):  
Jeongmin Seo ◽  
Dong-Yeop Shin ◽  
Youngil Koh ◽  
Inho Kim ◽  
Sung-Soo Yoon ◽  
...  

Background: Allogeneic stem cell transplantation (alloSCT) offers cure chance for various hematologic malignancies, but graft- versus-host disease (GVHD) remains a major impediment. Anti-thymocyte globulin (ATG) is used for prophylactic T-cell depletion and GVHD prevention, but there are no clear guidelines for the optimal dosing of ATG. It is suspected that for patients with low absolute lymphocyte counts (ALCs), current weight-based dosing of ATG can be excessive, which can result in profound T-cell depletion and poor transplant outcome. Methods: The objective of the study is to evaluate the association of low preconditioning ALC with outcomes in patients undergoing matched unrelated donor (MUD) alloSCT with reduced-intensity conditioning (RIC) and ATG. We conducted a single-center retrospective longitudinal cohort study of acute leukemia and myelodysplastic syndrome patients over 18 years old undergoing alloSCT. In total, 64 patients were included and dichotomized into lower ALC and higher ALC groups with the cutoff of 500/μl on D-7. Results: Patients with preconditioning ALC <500/μl were associated with shorter overall survival (OS) and higher infectious mortality. The incidence of acute GVHD and moderate-severe chronic GVHD as well as relapse rates did not differ according to preconditioning ALC. In multivariate analyses, low preconditioning ALC was recognized as an independent adverse prognostic factor for OS. Conclusion: Patients with lower ALC are exposed to excessive dose of ATG, leading to profound T-cell depletion that results in higher infectious mortality and shorter OS. Our results call for the implementation of more creative dosing regimens for patients with low preconditioning ALC.


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