Excessive Rate of Late Infections and Treatment Related Mortality Associated with the Use of Alemtuzumab in Reduced Intensity Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation: Results of a Prospective Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2230-2230
Author(s):  
Munira Shabbir ◽  
Luciano J Costa ◽  
Christine Schaub ◽  
Carrie Maxwell ◽  
Theo Fouts ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Acute Gvhd ◽  
Infectious Complications ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Group A ◽  
Related Mortality

Abstract Abstract 2230 Poster Board II-207 Background: Reduced intensity conditioning (RIC) for allogeneic hematopoietic stem cell (HSC) transplantation is a well established therapy for patients with advanced hematological malignancies who are not suitable candidates for fully myeloablative conditioning. The use of alemtuzumab as part of RIC has been associated with decrease in incidence and severity of graft versus host disease (GVHD), particularly in unrelated donor transplants. Methods: This is a single center, prospective study. Patients with relapsed or refractory hematological malignancies who were not candidates for fully myeloablative conditioning regimens received an non-alemtuzumab (nA) containing RIC regimen or an alemtuzumab-containing regimen (A) based on the use of a matched sibling or an allele-matched unrelated donor, respectively. Patients in the nA group were conditioned with either Fludarabine 30mg/m2/day for 5 days and total body irradiation 200cG or Fludarabine 25mg/m2/day for 5 days and Melphalan 70mg/m2/day for 2 days. Patients in the A group received alemtuzumab 20 mg/m2/day for 2 days, Fludarabine 30mg/m2/day for 5 days and Melphalan 70mg/m2/day for 2 days. All patients received peripheral blood HSC grafts. Prophylaxis against graft versus host disease with cyclosporine and mycophenolate mofetil as well as infectious disease prophylaxis and supportive care guidelines were standard across both groups. Results: From January 2003 to March 2009, 56 patients were enrolled in the study and 50 patients who actually received a HSCT are the subject of this analysis. Twenty nine patients were in group nA and 21 in group A. Median age of the patients in the entire cohort was 55 years (range 14-65). Eighteen patients had AML, 12 NHL, 8 MDS, 6 CML, 3 CLL and 3 MM. Twenty-three patients were considered to be at high-risk for post transplant relapse (45% of group nA vs. 47% of group A, P= 0.84). All patients in group nA had hematological engraftment while 2 patients in A (9.5%) failed to engraft. Despite the fact that all patients in group A received a transplant from an unrelated donor, the incidence of severe (grades C or D) acute GVHD was significantly higher in group nA (20.7% vs. 0%, P=0.03). Day 100 mortality was similar between the 2 groups (20.7% for nA vs 33.1% for A, P=0.31). Cumulative incidence of progression did not differ between the two groups (P=0.7) while the cumulative incidence of treatment related mortality was higher in group A (P=0.02, Figure 1). Both median overall survival (OS) (44.1 vs. 5.3 months; P=0.01, figure 2) and progression-free survival (PFS) (8.7 vs 5.3 months, P= 0.02) were superior in group nA. Cox regression analysis including conditioning regimen, age and risk of post-transplant relapse showed that conditioning with alemtuzumab was the only variable significantly associated with inferior OS (RR 2.8, P=0.009) and PFS (RR 2.42, P= 0.01). Group A had a higher incidence of late (after Day 100) infectious complications resulting in death (43% vs.10%, p=0.01). Conclusion: Even though alemtuzumab-based RIC in unrelated HSCT has a protective effect against acute GVHD and risk of D+100 TRM comparable with non-alemtuzumab containing RIC regimens in related donor transplant, its beneficial effect is overcome by excessive late infectious complications. Disclosures: Fouts: Genzime: Consultancy.

Outcomes of c Hematopoietic Stem Cell Transplantation (HCT) after Non-Myeloablative Conditioning in Relapsed, Refractory, or Transformed Indolent Non-Hodgkin Lymphoma (NHL).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3124-3124 ◽  
Author(s):  
Andrew R. Rezvani ◽  
Brenda M. Sandmaier ◽  
Barry Storer ◽  
Michael Maris ◽  
Edward Agura ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Aggressive Lymphoma ◽  
Optimal Timing ◽  
Unrelated Donor ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Allogeneic Hct ◽  
Grade 3

Abstract Sixty-two patients (pts) with chemotherapy-refractory indolent or transformed NHL were treated at 10 centers with allogeneic HCT from related (n=34) and unrelated (n=28) donors after 2 Gy total body irradiation with or without fludarabine. Diagnoses included follicular lymphoma (FL) (n=54, including 10 with grade 3 FL), small lymphocytic lymphoma (n=6), and marginal zone lymphoma (n=2). Median age was 54 years (range 33–66 years), and median time from diagnosis to HCT was 4.4 years (range 0.5–18.5 years). Sixteen pts had histologically documented transformation to diffuse aggressive lymphoma prior to HCT. Twenty-seven pts (44%) had failed autologous HCT. Disease status at the time of HCT was complete response (CR, n=16), partial response (PR, n=22), refractory (n=13), untested relapse (n=9), or unknown (n=2). Eleven of the 28 unrelated donor/recipient pairs (39%) had HLA mismatches: 2 at a single allele, 7 at a single antigen, and 2 at an antigen and an allele. One pt had non-fatal graft rejection from a 1-antigen-mismatched unrelated donor. Median follow-up of survivors after HCT was 36.6 months (range 2.3–60 months). Responses (CR [n=18] and PR [n=7]) were seen in 25 of 44 (57%) pts with evaluable disease prior to HCT, while 5 had stable disease, 9 progressed, and 5 were not evaluable due to early non-relapse mortality (NRM) on d27–d108. Two of 16 pts (13%) transplanted in CR relapsed; one was treated with donor lymphocyte infusion and achieved a persistent CR. The incidences of acute GVHD grades II–IV, III–IV, and chronic GVHD were 63%, 19%, and 53%, respectively. At 3 years, the risks of relapse/progression and NRM were 19% and 42%, respectively. There was a trend toward increased mortality with unrelated donors (HR 1.87 [0.9–3.7, p=0.08]). Progression-free and overall survival (PFS and OS) were significantly better in the non-transformed group (see tables 1 and 2). Table 1. Outcomes Non-transformed Transformed Relapse 6/46 (13%) 6/16 (38%) NRM 20/46 (43%) 6/16 (38%) 3-year OS 24/46 (52%) 4/16 (25%) 3-year PFS 20/46 (43%) 4/16 (25%) Table 2. Hazard Ratios (HR) for Transformed vs. Non-Transformed Pts HR (95% CI) p All-cause Mortality 2.39 (1.2–4.9) 0.02 Relapse/progression 4.75 (1.5–15) 0.01 Grade 3+ acute GVHD 1.84 (0.5–6.3) 0.35 Extensive chronic GVHD 1.96 (0.8–5.0) 0.18 Figure Figure Allogeneic HCT after non-myeloablative conditioning can produce durable responses and prolonged survival in pts with refractory indolent or transformed NHL. Pts transplanted before histologic transformation had significantly better outcomes. Future efforts will focus on reducing NRM and identifying optimal timing of HCT.

The Effect of Costimulatory Moleculars on Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4875-4875
Author(s):  
Zhenhua Qiao ◽  
Fang Ye ◽  
Lei Zu
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Group A ◽  
Group B

Abstract Objective: To explore the effect of costimulatory molecular and CD25 expressed on peripheral CD4+ T lymphocytes on graft-versus-host disease(GVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods: 1. The 21 patients who suffered of hematology diseases or malignant solid tumors and were underwent allo-HSCT and 10 normal individuals were enrolled in the study.2. For the sake of difference conditioning regimens we divided the 21 patients into two groups: patients undergoing non-myeloablative stem cell transplantation(NST) belonged to group A, others undergoing traditional myeloablative stem cell transplantation belonged to group B; we divided them into five groups for with GVHD or without GVHD and types of GVHD: group 1(group A with acute GVHD), group 2(group A with chronic GVHD), group 3(group B with acute GVHD), group 4(group B without GVHD), group 5(group A without GVHD).3. The levels of CD28, CD80, CD152 and CD25 expressions on peripheral CD4+ T lymphocytes were detected by three colors flow cytometry (FCM)in different time(before allo-HSCT,7days,14days,21days,30days after allo-HSCT, the time of GVHD and the time after GVHD treated).4.STR-PCR for detecting micro-satellites chimeras forming. Results: 1. All 21 patients achieved engraftment. By STR-PCR assay,12 cases formed complete chimeras(CC) and 9 cases formed mixed chimeras(MC). In group A,3 cases developed acute GVHD and 4 cases developed chronic GVHD; in group B,4 cases developed aGVHD. The incidence of GVHD and infection rates between group A and B has no difference(X2=3.711, P=0.144).2. Among these 21 cases,5 cases died:2 cases died of multiple organs function failure due to primary disease relapse,1 case died of bleeding in brain and 2 cases died of liver function failure for the sake of complicated with acute GVHD; others survive with disease free till present.3. The results of multivariate logistic regression models and Kaplan-Meier survival curves analyses showed: age, sex, infection, HLA-type, blood type, conditioning regiment and the times of absolute neutrophil counts and platelets recovering to normal, had no association with the incidence of GVHD;A multivariate COX survival function model analysis showed CD4CD152 and CD4CD25 are independent prognostic factors for GVHD(X2=13.128, P<0.0001).4. Patients with GVHD demonstrated higher CD4+CD28+ and CD4+CD80+ T cell levels than those without GVHD(P<0.01);patients with aGVHD demonstrated higher than those with cGVHD(P<0.05) and without GVHD(P<0.05); Patients with GVHD demonstrated lower CD4+CD152+ and CD4+CD25+ T cell levels than those without GVHD(P<0.01); the same result occurs between aGVHD and cGVHD and without GVHD. After effective treatment, unnormal CD4+CD28+, CD4+CD80+, CD4+CD152+ and CD4+CD25+ T cell levels recovered to the levels before transplantation. Conclusions: The incidences of GVHD between NST and traditional myeloablative stem cell transplantation had no difference. B7-CD28/CD152 costimulatory pathway plays a critical role in developing of GVHD. Peripheral CD4+CD28+, CD4+CD80+, CD4+CD152+ and CD4+CD25+ T cell levels were relative to recipient GVHD, especially CD4+CD152+ and CD4+CD25+ T cell levels. Down-grade CD4+CD28+ and CD4+CD80+ T cell levels and up-grade CD4+CD152+ and CD4+CD25+T cell levels could reduce the incidence of GVHD.

Tacrolimus Versus Cyclosporine for Graft-Versus-Host Disease Prophylaxis in Pediatric Patients Undergoing Matched Unrelated Donor Hematopoietic Stem Cell Transplants. A Pediatric Blood and Marrow Transplant Consortium Study..

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2883-2883 ◽  
Author(s):  
Mark P. Atlas ◽  
Gregory Yanik ◽  
Rakesh Goyal
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Grade Ii

Abstract Calcineurin inhibitors form the backbone of graft versus host disease (GVHD) prophylaxis in hematopoietic stem cell transplantation. In the adult literature tacrolimus was demonstrated superior to cyclosporine in preventing grade II–IV acute GVHD in both related and unrelated donor transplants; however, there is no data comparing their efficacy in the pediatric population. In a multi-institutional trial, we prospectively evaluated the clinical data on 102 patients receiving either cyclosporine/methotrexate or tacrolimus/methotrexate based prophylactic regimens for 6/6 matched unrelated donor, transplant. Conditioning regimens were fully ablative; no T-cell depletion was permitted; cord blood donors were excluded. Patients were required to receive either cyclosporine or tacrolimus, but the choice was per investigator preference. The two arms were reasonably balanced: 59.8% of patients received cyclosporine and 40.2% of patients received tacrolimus. Rates for maximum grade II–IV acute GVHD were 37.7% for cyclosporine and 39% for tacrolimus (p = 0.89). Rates for maximum grade III–IV acute GVHD were 19.6% for cyclosporine and 24.4% for tacrolimus (p = 0.57). Incidence of chronic GVHD in 97 evaluable patients was 37.9% in 58 patients who received cyclosporine and 35.8% in 39 patients who received tacrolimus (p = 0.84). Survival at 1 year post-transplant was similar in both groups: 59.2% for cyclosporine and 51.2% for tacrolimus (p= 0.31). Toxicity analysis is ongoing. In pediatric matched unrelated donor transplantation, the efficacy of tacrolimus/methotrexate and cyclosporine/methotrexate based regimens for prophylaxis of GVHD are not significantly different.

Reduced-Intensity Conditioning for Allogeneic Stem-Cell Transplantation (SCT) with Fludarabine and Intravenous Busulfan Is Associated with Improved Toxicity Profile and Longer Survival Than Conditioning with Fludarabine and Melphalan in Patients with Chemo-Sensitive Hematological Malignancies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2002-2002
Author(s):  
Avichai Shimoni ◽  
Izhar Hardan ◽  
Avital Rand ◽  
Noga Shem-Tov ◽  
Ronit Yerushalmi ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Graft Failure ◽  
Hematological Malignancies ◽  
Acute Gvhd ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Organ Toxicity ◽  
Increased Risk ◽  
Reduced Intensity ◽  
Grade Iii

Abstract Reduced-intensity conditioning (RIC) regimens are increasingly used in allogeneic SCT. They are more effective when the underlying malignancy is in remission at the time of SCT. Various RIC regimens have been designed, yet there is no defined data as to whether any of the regimens has an advantage over the others. To answer this question we retrospectively analyzed SCT outcomes in 100 consecutive patients (pts) given RIC for various hematological malignancies including AML/MDS (n=45), ALL (n=8), CML (n=6), multiple myeloma (MM, n=18), various lymphomas (n=19), others (n=4). All pts were considered not eligible for myeloablative conditioning and were required to have chemo-sensitive disease at SCT. The median age was 56 years (23–75). Donors were HLA-matched siblings (n=53) or matched unrelated (n=47). RIC consisted of fludarabine with intravenous busulfan (6.4 mg/kg; FB, n=62) or with melphalan (100–140 mg/m2; FM, n=38). The FB group included older pts; median age 59(23–75) compared with 51(27–66) years in the FM group (p&lt;0.001). The FB group included more pts with acute leukemia (66% vs 32%) while the FM group included more pts with MM (42% vs 2%, p&lt; 0.0001) and also more pts with a prior autologous SCT (42% vs. 21%, p=0.02). Donor type was not different between the regimens. 93 pts engrafted, 2 died early and 5 had primary graft failure, 3 after FB and 2 after FM (p=NS). The median time to engraftment was not different among groups. NCI grade III–IV organ toxicity occurred in 13 (21%) and 17 pts (45%) after FB and FM, resulting in 4 and 1 deaths, respectively (p=0.04). The cumulative incidence of acute GVHD grade II–IV were 20% and 43% (p=0.004) and the rates of grade III–IV were 6% and 19% (p=0.03), respectively. The cumulative incidence of chronic GVHD was 44%; not different between the regimens. The 1-year non-relapse mortality (NRM) rate was 10% after FB (6 pts; 1 graft failure, 1 organ toxicity, 2 GVHD, 2 infections) and 27% after FM (10 pts; 1 graft failure, 4 organ toxicity, 4 GVHD, 1 infection)(p=0.03). Relapse rate was not statistically different between the regimens; 38% and 50% after FB and FM, respectively (p=NS). With a median follow-up of 28 months (1–80), 58 pts are alive and 42 have died (18 NRM including 2 late events in the FB group, 24 of relapse). 43 FB and 15 FM recipients are alive with an estimated 3-yr survival rate of 59%(95CI, 43–75) and 26%(95CI, 8–44, p=0.007). Disease-free survival rates were 46%(95CI, 31–61) and 28%(95CI, 12–43, P=0.03), respectively. Multivariable analysis determined that FM conditioning was associated with shorter survival (HR, 2.9 (1.2–7.0), p=0.02) while SCT from an unrelated donor was of borderline significance (HR, 1.8 (1.0–3.3), p=0.06). Age, disease type and prior autologous SCT were not predictive of survival in this cohort. In conclusion, there are marked differences in SCT outcomes between RIC regimens that are theoretically equivalent in dose intensity. The FM regimen in the doses used is more toxic. It was associated with higher incidence of NRM due to increased risk of both organ toxicity and acute GVHD. FM offered no advantage in disease control in pts with chemo-sensitive disease, thus reduced toxicity with FB translated into improved survival. These observations merit further study in more homogeneous pt population and in prospective studies.

The FcγRllla Polymorphism Correlates with Chronic Graft-Versus-Host Disease and Treatment Related Mortality.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2237-2237
Author(s):  
Akiyoshi Takami ◽  
J. Luis Espinoza ◽  
Ken Ishiyama ◽  
Satomi Ohyachi ◽  
Yuki Kato ◽  
...  
Keyword(s):  
Acute Gvhd ◽  
Cord Blood Transplantation ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Graft Versus Host ◽  
Blood Transplantation ◽  
High Risk Disease ◽  
Related Donor ◽  
Independent Risk Factors ◽  
Related Mortality

Abstract The FcγRllla (FCGR3A) 158V/V allotype displays a higher antibody-dependent cellular cytotoxicity compared to the FCGR3A-158V/F or 158F/F allotype, leading to susceptibility to rheumatoid arthritis, better clinical response to rituximab in NHL, and lower risk of periodontitis. We tested the hypothesis that FCGR3A polymorphism influences the development of GVHD and GVL, and TRM. The FCGR3A-158V/F genotype was determined in 49 recipient and donor pairs who underwent HLA-matched SCT in our institute. Subjects with the recipient FCGR3A-158V/V allotype and the donor FCGRA-158V/V allotype were almost one-third and twice as likely to develop chronic GVHD respectively (Table 1). The recipients with the FCGR3A-158V/V allotype had a 60% increase in probability of 3-year TRM. Multivariate analysis showed that the recipient FCGR3A-158V/V allotype and the donor FCGRA-158V/V allotype were independent risk factors for chronic GVHD (HR = 0.8 and 1.2, respectively), as well as the unrelated donor BMT (HR = 1.6) and the related donor PBSCT (HR = 2.4). The recipient FCGR3A-158V/V was an independent predictor for 3-year TRM (HR = 4.0) with the high risk disease (HR = 3.0) and the cord blood transplantation (HR = 5.0). We conclude that the recipient and donor FCGR3A polymorphism is associated with the development of chronic GVHD and TRM after HLA-matched SCT. These findings could therefore be useful in selecting the donor and creating therapeutic strategies for improving the final outcome of allogeneic SCT. Besides, these raise the question of whether the genetic risk factor in a recipient might also be involved in the mechanisms of chronic GVHD. Table 1 FCGR3A allotype 2–4 acute GVHD(HR) Chronic GVHD (HR) 3 YR TRM (HR) *P&lt;0.05 Recipient FCGR3A-158V/V 46% (1.2) 17%* (0.8*) 72%* (4.0*) Recipient FCGR3A-158V/F or 158F/F 39% 57% 44% Donor FCGR3A-158V/V 46% (1.1) 67%* (1.2*) 43% (0.5) Donor FCGR3A-158V/F or 158F/F 38% 30% 50%

scholarly journals The role of HLA-DPB1 disparity in the development of acute graft-versus- host disease following unrelated donor marrow transplantation

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1923-1932 ◽  
Author(s):  
EW Petersdorf ◽  
AG Smith ◽  
EM Mickelson ◽  
GM Longton ◽  
C Anasetti ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Unrelated Donor ◽  
Host Disease ◽  
Graft Versus Host ◽  
Group A ◽  
Group B ◽  
Acute Graft

Abstract The role of HLA-DPB1 disparity in the development of acute graft-versus- host disease (GVHD) following unrelated donor (URD) marrow transplantation is unknown. We studied 129 patients who underwent marrow transplantation from HLA-A, -B, -DRB, and -DQB matched URDs to determine whether matching for HLA-DPB1 alleles significantly decreased the risk of developing acute GVHD. HLA-DPB1 alleles were determined by sequence-specific oligonucleotide hybridization and by the number of patient DPB1 alleles not shared by the donor scored. The Kaplan-Meier probability of developing grades II to IV acute GVHD was determined for patients incompatible for zero (group A), one (group B), or two (group C) DPB1 alleles. Of the 129 pairs, there was no recipient DPB1 incompatibility in 28 (22%), one DPB1 mismatch in 72 (56%), and two DPB1 mismatches in 29 (22%). The probability of grades II to IV acute GVHD was 0.69 (0.50, 0.86) for group A, 0.83 (0.73, 0.91) for group B, and 0.72 (0.56, 0.87) for group C (P = .63). These results indicate that matching patients and unrelated donors for HLA-A, -B, -DRB, and - DQB does not predict for matching at DPB1. However, recipient incompatibility for DPB1 alleles does not detectably influence the risk of acute GVHD. Therefore, HLA-DP disparity should not be used as an exclusion criterion for donor selection in unrelated marrow transplantation.

Reduced Intensity Conditioning Compared With Myeloablative Conditioning Using Unrelated Donor Transplants in Patients With Acute Myeloid Leukemia

2009 ◽  
Vol 27 (27) ◽  
pp. 4570-4577 ◽  
Author(s):  
Olle Ringdén ◽  
Myriam Labopin ◽  
Gerhard Ehninger ◽  
Dietger Niederwieser ◽  
Richard Olsson ◽  
...  
Keyword(s):  
Conditioning Regimen ◽  
Multivariable Analysis ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Myeloablative Conditioning ◽  
Peripheral Blood Stem Cells ◽  
Hematopoietic Stem ◽  
Blood Stem Cells ◽  
Total Body ◽  
Reduced Intensity

Purpose Reduced intensity conditioning regimen (RIC) is increasingly used in hematopoietic stem cell transplantation (HSCT). Unrelated donor (UD) transplants have more complications. We wanted to examine if RIC is a valid treatment option using UD in acute myeloblastic leukemia (AML). Patients and Methods Between 1999 and 2005, 401 patients with AML were treated with RIC and 1,154 received myeloablative conditioning (MAC), using UD and reported to the European Group for Blood and Marrow Transplantation Registry. Patients < and ≥ 50 years of age were analyzed separately. Results Patients receiving RIC were older, received transplants more recently, received peripheral blood stem cells more frequently, and were treated with total-body irradiation less often. In multivariable analysis, in patients younger than 50 years of age, nonrelapse mortality (NRM) was similar using RIC (hazard ratio [HR], 0.85; P = .41), relapse was increased (HR, 1.46; P = .02) and leukemia-free survival (LFS) was the same (HR, 0.88; P = .28), as compared with MAC. In patients ≥ 50 years of age, NRM was decreased in the RIC group (HR, 0.64; P = .04), relapse probability was not significantly different (HR, 1.34; P = .16) and LFS was similar (HR, 1.04; P = .79) compared with MAC. Conclusion RIC-UD transplants are associated with higher relapse in AML patients younger than 50 years of age and decreased NRM in those ≥ 50 years compared with MAC-UD. LFS was similar after both conditioning regimens, regardless of age. Therefore, RIC-UD extend the use of allotransplants for elderly patients and strategies that decrease relapse should be considered mainly in younger patients with AML.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) with Different Intensity Conditioning Regimens in Children with Very High Risk Acute Lymphoblastic Leukemia (VHR ALL): A Single-Center Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2050-2050
Author(s):  
Elena Vladimirovna Semenova ◽  
Olesia V Paina ◽  
Zhemal Zarifovna Rakhmanova ◽  
Polina Valerievna Kozhokar ◽  
Anastasia S Frolova ◽  
...  
Keyword(s):  
High Risk ◽  
Performance Status ◽  
Poor Performance ◽  
Poor Performance Status ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Very High ◽  
Reduced Intensity

Background: Allo-HSCT with myeloablative conditioning (MAC) has traditionally been performed in patients with ALL and has been associated with significant transplant-related morbidity and mortality. Reduced-intensity conditioning (RIC) is used in patients not eligible for conventional conditioning therapy due to poor performance status and severe toxic complications after previous chemotherapy. RIC is a well-established treatment strategy in adult patients with comorbidities or in elderly patients. In contrast to the adults, the RIC pediatric experience is still sparse. The aim: to compare efficacy of reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) for allo-HSCT in children suffering from very high risk (VHR) ALL. Patients and methods: This was a retrospective analysis performed in 233 patients (pts) with ALL (age - from 4 month till 18 y.o. (mediana 11 y.o.)), who received allo-HSCT at R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation between 12/2000 and 12/2017. MAC (busulfan or treosulphan containing) was used in 159 pts: 1st CR - 26 pts, 2nd CR -57 pts, 3rd or 4th CR 23 - pts, relapse -53 pts. Allo-HSCT with RIC was performed in 74 pts: 1st CR - 14 pts, 2nd CR -29 pts, 3rd or 4th CR - 12 pts, relapse -20 pts. RIC consisted of fludarabine (30 mg/m2/d x 5 days) + melfalan (70 mg/m2/d x 2 days) or fludarabine (30 mg/m2/d x 5 days) + busulfan (4 mg/kg/d x 2 days). The disease status was not different between groups (p=0.674) Indication for RIC allo-HSCT was poor performance status (Lanskoy/Karnovsky<70%), organ dysfunction due to previous therapy or infectioous complications at the moment of allo-HSCT. Allo-HSCT from matched related donor was performed in 41 pts, from matched unrelated donor - in 131 pts, haploidentical - in 61 pts. Post-transplant Cy was included in GVHD prophylaxis regimens in 102 pts (44%). Results: Median follow-up was 5 years for МАС, 4.5 years for RIC. In both groups the median time to neutrophil engraftment >=0,5x109/l was D+18 (range D+8-48). Transplant engraftment was observed in 64 pts (86%) after RIC and 150 pts (93%) after MAC (p=0,224). OS pts after RIC allo-HSCT performed in 1 CR 70% and after MAC - 85% (p=0,043), in 2 CR 56% after RIC and 49% after MAC (p=0,436), in 3 or 4 CR 34% after RIC and 25% after MAC (p=0,394). OS in patients with active disease was 16% in RIC-group and 18% in MAC-group (p=0,432). The transplant-related mortality rate was 18% after RIC and 20% after MAC (p=0,40). Risk of relapse was 37% after RIC and 42% after MAC (p=0,39). Acute GVHD II-IVgr developed in 32% pts after RIC and 33% after MAC (p=0,883), early infections were diagnosed in 63% in RIC-group, and 59% in MAC-group (p=0,356). Early toxic complications were observed (CTC): mucositis III-IV gr in 13% pts after RIC and in 54% pts after MAC (p=0,001), nephrotoxicity in 7% pts and in 21% pts (p=0,042), hepatitis gr II-III in 24% pts and in 57% pts, respectively (p=0,034), neurological complications in 22% pts and 42% pts, resp. (p=0,046). Conclusion: RIC allo-HSCT of VHR ALL in 2,3 or 4 CR pts ≤ 18 y.o. is effective and comparable with MAC allo-HSCT. Early toxic complications after RIC were less frequent. Possibly, the use of RIC can maintain efficacy while minimizing regimen-related toxicity in children who have undergone previous intensive treatment. Disclosures Moiseev: Pfizer: Other: Travel grants; BMS: Other: Travel grants; MSD: Other: Travel grants; Novartis: Consultancy, Honoraria, Other: Travel grants, Speakers Bureau; Celgene: Consultancy, Other: Travel grants; Takeda: Other: Travel grants.

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