scholarly journals Effect of graft source on mismatched unrelated donor hemopoietic stem cell transplantation after reduced intensity conditioning

Leukemia ◽  
2013 ◽  
Vol 27 (11) ◽  
pp. 2113-2117 ◽  
Author(s):  
F Malard ◽  
S Fürst ◽  
M Loirat ◽  
P Chevallier ◽  
J El-Cheikh ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hemopoietic Stem Cell ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Hemopoietic Stem Cell Transplantation ◽  
Reduced Intensity

scholarly journals Association between preconditioning absolute lymphocyte count and transplant outcomes in patients undergoing matched unrelated donor allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning and anti-thymocyte globulin

2021 ◽  
Vol 12 ◽  
pp. 204062072110637
Author(s):  
Jeongmin Seo ◽  
Dong-Yeop Shin ◽  
Youngil Koh ◽  
Inho Kim ◽  
Sung-Soo Yoon ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Matched Unrelated Donor ◽  
T Cell Depletion ◽  
Reduced Intensity

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.

Results of Genoidentical Hemopoietic Stem Cell Transplantation With Reduced Intensity Conditioning for Acute Myelocytic Leukemia: Higher Doses of Stem Cells Infused Benefit Patients Receiving Transplants in Second Remission or Beyond—The Acute Leukemia Working Party of the European Cooperative Group for Blood and Marrow Transplantation

2006 ◽  
Vol 24 (24) ◽  
pp. 3959-3966 ◽  
Author(s):  
Norbert-Claude Gorin ◽  
Myriam Labopin ◽  
Jean-Michel Boiron ◽  
Niklas Theorin ◽  
Tim Littlewood ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hemopoietic Stem Cell ◽  
Acute Myelocytic Leukemia ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Cell Dose ◽  
Myelocytic Leukemia ◽  
Reduced Intensity

Purpose Nucleated cell dose is an important and modifiable factor in hematopoietic stem cell transplantation (HSCT), however its association with outcomes in the context of reduced intensity conditioning regimen (RIC) HSCT for adults with acute myelocytic leukemia (AML) is not known. Patients and Methods From 1998 to 2003, 253 patients with de novo AML, received transplants with RIC and peripheral blood from a genoidentical donor. Median age was 55 years (range, 18 to 72) and the median follow-up was 17 months (range, 2 to 67). One hundred forty one patients received transplants in first remission (CR1), 47 received transplants in second remission (CR2), and 65 patients received transplants in a more advanced phase. Fludarabin-based RIC was used in 91% of patients and low-dose (< 4 Gy) total-body radiation in 23% of patients. The median nucleated and CD34 cell dose infused were 9.1× 108/kg and 5.8× 106/kg, respectively. Results Overall, 2-year leukemia-free survival (LFS) was 41% ± 4% and it was 46% ± 5% for patients receiving a higher cell dose (> 9.1× 108/kg) and 37% ± 5% for the remainders (P = .03). Higher cell doses exclusively benefited patients who received transplantations in CR2 or beyond, with LFS of 47 ± 8 versus 20 ± 8, with no detectable effect for patients who received transplants in CR1. In a multivariate analysis of the overall patient population, higher nucleated cell dose cells were associated with higher LFS (P = .04), higher incidence of chronic graft-versus-host disease (P = .01), and there was a trend towards a lower relapse incidence (P = .06). Interestingly, CD34+ cell dose was not associated with any outcomes. Conclusion Nucleated cell dose is an important factor that can be modified to improve results of RIC for patients with AML transplanted later than in CR1.

High Rates of Early Donor Chimerism and Low Risk of Chronic GVHD Can Be Achieved in Poor Risk Patients Undergoing Unrelated Donor Stem Cell Transplantation Using a Reduced Intensity Conditioning Regimen Incorporating Fludarabine, Busulfan, and Rabbit ATG.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5080-5080
Author(s):  
Mehdi Hamadani ◽  
Patrick Elder ◽  
Farrukh Awan ◽  
David Krugh ◽  
William Blum ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Post Transplant ◽  
Ebv Reactivation ◽  
Risk Patients ◽  
Reduced Intensity

Abstract Reduced intensity conditioning (RIC) regimens are increasingly used for allogeneic stem cell transplantation (allo-SCT) in patient groups with relative contraindications for transplantation since they promote effective engraftment of donor cells with minimal regimen related toxicity. However, following unrelated donor (URD) transplantation, high rates of acute and extensive chronic GVHD have mitigated the overall benefits of this approach. We pursued a strategy designed to enhance early full donor hematopoietic chimerism while potentially reducing the risk of severe acute and extensive chronic GVHD using an RIC regimen containing fludarabine (F), busulfan (B), rabbit antithymocyte globulin (A) (FBA) followed by URD SCT in 30 consecutive high risk patients (pts). Criteria for selection included advanced age (>55yrs), prior autograft, and/or high co-morbidity index (median 2, range 0–4). There were 24 male and 6 female pts with a median age of 53 years (range 22–66yrs). Diagnoses included AML (N=10), NHL (N=7), Hodgkin’s lymphoma (N=6), advanced CML (N=4), and advanced CLL (N=4). Nine pts had previously undergone autologous SCT. 43% had a Karnofsky performance status of 70 or 80% at the time of transplant. 80% were matched with their donor at HLA-A, B, C, and DRB1 by high-resolution DNA typing, while 3 were mismatched at 1 antigen and 3 mismatched at 1 or 2 alleles. All pts were conditioned with F (30 mg/m2/day, days −7 to −3), B (0.8 mg/kg/dose IV x 8 doses) and A (2.5 mg/kg/day, days −4 to −2) followed by micro-dose methotrexate and tacrolimus. Stem cell source included peripheral blood (n=26) or bone marrow (n=4). All pts engrafted neutrophils and platelets promptly (median 15 and 16 days, respectively). There were no primary graft failures. Rates of grade II-IV and III-IV acute GVHD were 43% (n=13) and 23% (n=7) respectively. Nine pts (30%) developed chronic GVHD but extensive chronic GVHD was seen in only 10% (n=3). Day 100 TRM was 10% (n=3). Causes of death included disease progression=2, post-transplant lymphoproliferative disorder (PTLD) =1 and sepsis=1. CMV and EBV reactivation occurred in 30% (n=9) and 20% (n=6) respectively. 2 pts developed PTLD requiring rituximab. Three pts had BK-virus associated hemorrhagic cystitis. Lineage-specific chimerism analysis showed 100% donor CD33+ at all time points (days 30, 60, 100) and median donor CD3+ chimerism of 94% at day +30 and 100% at day +100. One patient had secondary graft failure. 23 pts (76%) were in CR after SCT. The median follow-up of surviving patients is 6 months (range 1–32 months). Kaplan-Meier estimates of overall survival (OS) and progression free survival (PFS) at 1year are 62% and 43% respectively. Using the Log-Rank test, OS (P=0.95) and PFS (P=0.65) was not statistically significant between recipients of matched and mismatched grafts. In conclusion, this approach using FBA and a tacrolimus based GVHD prophylaxis achieved rapid donor chimerism and a favorably low incidence of TRM, acute, and chronic GVHD despite being tested in a poor risk group of pts. Although rates of infectious complications were within expected ranges, the rate of both EBV reactivation and disease relapse warrant further exploration of this approach using lower doses of ATG (e.g. 5–6mg/kg total dose) combined with post transplant immunomodulation.

Outcomes After a Sequential Clofarabine/Arac-C Chemotherapy Followed By Reduced-Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (allo-SCT) In Pediatrics Patients With JMML Or Primary/Relapsed Refractory AML: A Pilot Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5460-5460
Author(s):  
Grain Audrey ◽  
Anne Sirvent ◽  
Marion Strullu ◽  
Francoise Mechinaud ◽  
Mohamad Mohty ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Number Of Patients ◽  
Sequential Regimen ◽  
Reduced Intensity ◽  
Refractory Aml

Abstract Introduction The FLAMSA sequential treatment with chemotherapy followed by reduced-intensity conditioning (RIC) for allogeneic stem cell transplantation (allo-SCT) has been introduced few years ago for adult refractory acute myeloid leukemia (AML) showing high activity and relatively good survivals in this particular setting (Schmid, Blood, 2006). There is no study at our knowledge reporting the results of the sequential approach in pediatric refractory AML patients. Here we report our own experience in 6 children using a debulking chemotherapy combining clofarabine and Ara-C followed by RIC before allo-SCT. Patients and Methods These preliminary results included 3 males and 3 females with a median age of 7 years (range: 4-11). All cases had received a sequential regimen before allo-SCT at the CHU of Nantes (n=5) or at the CHU of Montpellier (n=1) for primary refractory AML (n=1), refractory relapsed AML (n=3), slow responder relapsed AML (n=1) and blastic JMML (n=1). Sequential regimen consisted of 1) clofarabine 30 mg/m²/d days-13 to -9, Ara-C 1g/m²/d days-13 to-9 followed by RIC combining cyclophosphamide 60 mg/kg/d day-5, iv Busulfan 3.2 mg/Kg/d days -4 to -3 and ATG 2.5 mg/Kg/d days -3 to -2 in 5 patients and 2) clofarabine 30 mg/m²/d days-13 to -9, Ara-C 1g/m²/d days-13 to-9 followed by RIC total body irradiation 4 grays day-5, cyclophosphamide 40 mg/Kg/d days -4 to -3, and ATG 2.5 mg/Kg/d days -3 to -2 in 1 patient. One patient received a graft from a sibling donor while the five other patients received a graft from an unrelated donor (10/10 n=3; 9/10 n=2). All patients received PBSC as stem cells graft. Ciclosporine alone was used in case of related donor while ciclosporin+MMF were used in case of an unrelated donor. Results Engraftment was observed in 4 patients (67%) and 3 patients out of the 5 refractory cases achieved complete remission (CR) after transplant. The 2 patients who had an autologous reconstitution, relapsed and died rapidly. Considering the 4 patients achieving full engraftment and CR, only one relapsed at day+60 and died of relapse. The three other patients are alive in CR at +12, +35 and +51 months post-transplant. Conclusion To our knowledge, this is the first report of a sequential allo-SCT approach for refractory pediatric AML patients. Although the number of patients is limited in our cohort, the results showed here are very encouraging as half of the patients are alive in CR with full engraftment. These results have to be confirmed prospectively. Disclosures: No relevant conflicts of interest to declare.

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