Unrelated Allogeneic Stem Cell Transplantation with Myeloablative Preparative Regimen for Adult Patients with Acute Lymphoblastic Leukemia in CR: A Survey from the European Group for Blood and Marrow Transplantation (EBMT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3112-3112
Author(s):  
Nadezda Basara ◽  
Myriam Labopin ◽  
Tapani Ruutu ◽  
Axel Zander ◽  
Renate Arnold ◽  
...  

Abstract Data from the EBMT indicate that approximately 46% of Unrelated Allogeneic Stem Cell Transplantation (UD-SCT) in Europe utilize peripheral blood (PB) and 54% bone marrow (BM) as a graft source for adult patients with ALL since January 1998. However, prospective randomized trials comparing the two stem cell sources are lacking. This study describes the results of 782 adult patients with ALL in remission (422 BM and 360 PB) transplanted in different centers affiliated with the EBMT from 1998 to 2004 with an HLA identical unrelated donor (HLA-A and -B low resolution and HLA-DRB1 allelic typing). Median age was 27 years for BM (range 16–63, male 60%) and 30 years for PB (range16–63, male 62%), respectively. Fifty four (54%) and 64% of patients were transplanted in first complete remission (CR1) in the BM and PB groups, respectively. The frequency of female donor to male recipient was 18% in the BM and 15% in the PB group. Total Body Irradiation (TBI)-based preparative regimens were given in 85% and 88% of patients in the BM and PB group respectively. Graft-versus-Host Disease (GvHD) prophylaxis consisted of cyclosporine A (CsA) (6% and 4%), CsA and methotrexate (77% and 58%) or in vitroT-cell depletion (17% and 38% in BM and PB group, respectively). With the median follow-up of 17 (range 1–92) and 11,3 (range 1–71) months, the incidence of GvHD grade II–IV was 37% in the BM group and 39% in the PB group (p=0.39). Probabilities of LFS, TRM and relapse were calculated using the Kaplan-Meier estimate. LFS was 45+/−3% vs 36+/−3% (p=0.04) transplant related mortality (TRM) was 33+/−2% and 39+/−3(p=0.29 while incidence of relapse was 32+/−3% and 41+/−4%(p=0.06), in the BM and PB groups respectively. Two years leukemia-free survival (LFS) for the patients transplanted in CR1 was 48% (BM) and 42% (PB, p=0.48). However, 2-years LFS for patients transplanted in CR2 or CR3 was significantly higher in the BM compared to the PB group (42% and 26%, p<0.004). The probability of relapse was significantly lower in BM compared to PB (32% vs 54%, p<0.001) without there being a detectable difference in TRM at 2 years (38% vs 43%, p= 0.31). In conclusion, the results of this retrospective comparative study confirm that UD-SCT with BM and PB as a graft source have similar results for patients in CR1. However, patients transplanted in CR2 or CR3 with a bone marrow graft, have decreased relapse incidence and better LFS, probably reflecting disease and transplant related differences compared to PB transplants such as in vitro T cell depletion more used in those transplants.

2017 ◽  
Vol 9 (3) ◽  
Author(s):  
Federica Cattina ◽  
Simona Bernardi ◽  
Vilma Mantovani ◽  
Eleonora Toffoletti ◽  
Alessandra Santoro ◽  
...  

The outcome of patients underwent to allogeneic stem cell transplantation (allo- SCT) is closely related to graft versus host disease (GvHD) and graft versus leukemia (GvL) effects which can be mediated by mHAgs. 23 mHAgs have been identified and reported to be differently correlated with GVHD or GVL and the aim of this work was develop a method to genotype the mHAgs described so far. For this study we used MALDI-TOF iPLEX Gold Mass Array technology. We tested 46 donor/recipient matched pairs that underwent allo-SCT because of Philadelphia positive (Ph+) chronic myeloid leukemia (n=29) or Ph+ acute lymphoblastic leukemia (n=17). Our data show that sibling pairs had a lesser number of mHAgs mismatches compared to MUD pairs. Notably, donor/recipient genomic mismatch on DPH1 was correlated with an increased risk of acute GvHD and LB-ADIR-1R mismatch on graft versus host direction was correlated with a better RFS with no increase of GvHD risk. Our work provides a simple, accurate and highly automatable method for mHAgs genotyping and suggest the role of mHAgs in addressing the immune reaction between donor and host.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5445-5445
Author(s):  
Takeshi Kobayashi ◽  
Takuya Yamashita ◽  
Miwa Sakai ◽  
Yoshiki Okuyama ◽  
Kazuteru Ohashi ◽  
...  

Abstract Purpose We report the outcomes of allogeneic stem cell transplantation (SCT) for the patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) in a single center. Patients and Methods Between August 1993 and March 2005, 36 patients with Ph+ALL received SCT at Tokyo Metropolitan Komagome Hospital. The median age was 41 years (range; 17 to 60 years). All patients received myeloablative conditioning regimen (cytosine arabinoside, cyclophosphamide and fractionated 12Gy total-body irradiation). Stem cell source of SCT was 14 related donors (bone marrow [n=9] and peripheral blood stem cell [n=5]) and 22 unrelated donors (bone marrow [n=13] and cord blood [n=9]). Results Seventeen (47%) of 36 patients are alive at a median of 2.16 years (range; 1.0 to 3.3 years) after transplantation. Three years overall survival (OS) and disease free survival (DFS) for all patients are 42.3% and 35.4%, respectively. Three years OS and DFS are 55.4% and 46.4% for the 24 patients in complete remission (CR) at transplantation, while 36.4% (p&lt;0.001) and 16.7% (p&lt;0.01) for the 12 patients in non-CR, respectively. Stem cell source and patients age do not affect the outcomes. The higher white blood cell counts at diagnosis are associated with poor OS (p=0.003). The median duration from diagnosis to SCT is 7 months (range; 3 to 29 months). Three years OS of the patients who received SCT within 7 months from diagnosis is better than that of the others (59.3% vs. 31.1%, p=0.019). Conclusion This analysis suggests that shorter duration between diagnosis and transplantation improve the clinical outcomes of SCT for Ph+ALL, especially performed in CR.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3032-3032
Author(s):  
John Kuruvilla ◽  
Qikun Bao ◽  
Mira Goldberg ◽  
Vikas Gupta ◽  
Thomas L. Kiss ◽  
...  

Abstract Introduction Allogeneic stem cell transplantation (Allo-SCT) remains an option for patients with chronic lymphocytic lymphoma (CLL). Our program employs a strategy using allo-SCT for patients (pts) with high risk disease based on clinical characteristics and prior therapy. We performed a retrospective analysis to examine long-term disease control and treatment toxicity. Methods A total of 52 patients (pts) are included who underwent allo-SCT at our institution between Aug 1989 and Dec 2005. Patients were in a chemosensitive remission at the time of SCT. The conditioning regimen consisted of busulfan (1 mg/kg PO q6h X4 days between 1989–200 and 3.2 mg/kg IV daily X 4days subsequently) and cyclophosphamide 60 mg/kg X 2 days. Cyclophosphamide 60 mg/kg X 2 days and TBI 12 Gy was used for unrelated donor SCT. Reduced intensity conditioning (RIC) SCT were typically performed with Fludarabine 50 mg/m2 for 4 days and 2 Gy TBI. GVHD prophylaxis was with cyclosporine A and methotrexate. Results There were 34 males and 18 females. The median age at the time of transplant was 51 years (range 26 to 65). Histologic subtype was: CLL and/or small lymphocytic lymphoma (SLL); 48 and T-prolymphocytic leukemia (PLL): 4. The median number of prior chemotherapy regimens was 3 (range 1 – 10) and was unavailable in 16. Prior chemotherapies included: anthracycline-based: 24, prior purine analog: 32, prior platinum-based: 8, prior auto-SCT: 1, prior rituximab: 5. The median time from diagnosis to allo-SCT was 58 months (range 5 – 260). 10 pts underwent RIC SCT. Graft source was: matched sibling (MSD) bone marrow (BM): 18, MSD peripheral blood stem cells (PBSC): 20, Mismatch related (MMRD) bone marrow (BM): 1, MRD PBSC: 4, matched unrelated donor (MUD) BM: 8, MUD PBSC: 1. At 5 years, the overall survival of the entire cohort is 51% (95% confidence intervals: 34 – 68%) with two long-term survivors of 14 and 17 years. Treatment-related mortality (TRM) was 20 of 52 pts (38%). 4 pts have relapsed ((8% of total cohort) and non-relapse mortality was 1 pt (2%). Overall survival by intensity of SCT conditioning regimen was not significant (p=0.3). TRM was similar in pts who received fully myeloablative SCT (40% vs. 20% in RICSCT group, p=0.29). Conclusions Acceptable survival post-SCT is possible using an allo-SCT strategy in CLL. However, TRM remains high in this group of heavily pre-treated patients with a median age of over 50 that predominantly received fully myeloablative allo-SCT. Due to small sample size, the potential benefit of reduced TRM with RICSCT cannot be demonstrated. Ideally, allo-SCT should be considered earlier in the course of the disease based on risk stratification utilizing traditional risk factors and modern prognostic factors such as FISH studies and novel markers.


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