scholarly journals Comparison of Transplant Outcomes in Patients with Acute Lymphoblastic Leukemia after Haploidentical Transplant with Post-Transplant Cyclophosphamide or Matched Unrelated Donor Transplant

2020 ◽  
Vol 26 (3) ◽  
pp. S58-S59
Author(s):  
Monzr M. Al Malki ◽  
Dongyun Yang ◽  
Myriam Labopin ◽  
Boris Afanasyev ◽  
Emanuele Angelucci ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Post Transplant ◽  
Transplant Outcomes ◽  
Donor Transplant

scholarly journals Chidamide-Containing Conditioning Allogenic Hematopoietic Stem Cell Transplantation Improves Prognosis of Acute Lymphoblastic Leukemia with Pre-Transplant Response Less Than Complete Remission

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3366-3366
Author(s):  
Jie Ji ◽  
Tian Dong ◽  
Pu Kuang ◽  
Zhigang Liu ◽  
Jiazhuo Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Blast Cells ◽  
Active Disease ◽  
Donor Transplant

Abstract Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option currently offered to patients with high-risk or relapsed acute lymphoblastic leukemia (ALL). However, active disease or minimal residual disease (MRD) prior to HSCT is associated with early relapse and poor prognosis with long-term survival less than 30%. We have confirmed that chidamide, a selective histone deacetylase inhibitor (HDACi), work synergistically with cytotoxic agents such as combination of cladribine, gemcitabine and busulfan as conditioning therapy against lymphocytic malignancies. Here, we conducted a clinical trial to evaluate the efficacy of chidamide containing conditioning allo-HSCT in patients with these high-risk ALLs. Methods: Patients with active ALL or MRD received a myeloablative conditioning consisting of chidamide, fludarabine, cytarabine and busulfan (ChiFAB), followed by infusion of peripheral blood hematopoietic stem cells from related or unrelated donors. The ChiFAB was administered as following: chidamide was given orally at 20 mg twice weekly started from D-7 for 3 weeks; fludarabine was given intravenously at 30 mg/m2 D-6 to D-2; cytarabine was given 4 hours after the finish of fludarabine at 1 g/m2 D-6 to D-2; and busulfan was given intravenously once daily at 3.2 mg/kg D-6 to -3. Prophylaxis of acute graft-versus-host-disease were posttransplant cyclophosphamide plus cyclosporine for matched donor transplants, and additional post-transplant anti-thymocyte globulin and mycophenolate mofetil for haplo-HSCT. Donor lymphocyte infusion was not routinely administered in this trial. Results: Twenty-four patients were enrolled with median age of 24.5 (16-61 years). Male to female ratio was 3:1. Six (25%) had a diagnosis of Philadelphia positive acute B cell lymphoblastic leukemia (Ph+B-ALL), 8 (33.3%) had Ph-B-ALL, and 10 (41.7%) had T-ALL. Nineteen (79.2%) patients were MRD positive (blast cells <5% in the bone marrow), while five (20.8%) were with active disease (blast cells ≥5%). Eleven (45.8%) patients underwent matched sibling donor transplant, 4 (16.7%) underwent matched unrelated donor transplant, and 9 (37.5%) received haplo-HSCT. Neutrophils and platelets engrafted at a median of 14 days (12-20 days) and 16 days (12-46 days) post-transplant, respectively. Twenty (83.3%) patients reached MRD negative at 30 days. The median follow-up time of the whole cohort was 9.2 months (2-43.8), estimated 1-year progression free survival (PFS) and overall survival (OS) are 53.1% and 59.4% (Figure-1 A&B). For patients with MRD or active disease, estimated 1-year PFS are 67% and 0% (Figure-1 C), and estimated 1-year OS of these 2 groups of patients are 67.7% and 30% (Figure-1D), respectively. Only one patient (4.2%) developed II° aGvHD within 100 days post-transplant (Figure-1 E). The incidence of non-relapse mortality is 24.6% (Figure -1 F). Conclusions: Chidamide-containing conditioning allo-HSCT may improve the prognosis of ALL with MRD. Figure 1. Figure 1. Disclosures Liu: West China Hospital of Sichuan University: Employment.

scholarly journals Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jaime Sanz ◽  
Jacques-Emmanuel Galimard ◽  
Myriam Labopin ◽  
Boris Afanasyev ◽  
Moiseev Ivan Sergeevich ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cumulative Incidence ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Donor Type ◽  
Matched Sibling ◽  
The Impact

Abstract Background There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). Methods We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n = 78), matched unrelated (MUD) (n = 94) and haploidentical family (Haplo) (n = 297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. Results Median age of patients was 38 years (range 18–76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II–IV and III–IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p = 0.4); 13%, 15%, and 15% (p = 0.8); 35%, 50%, and 42% (p = 0.01); and 11%, 17%, and 21% (p = 0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p = 0.8); and 21%, 18%, and 21% (p = 0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p = 0.8); 66%, 69%, and 62% (p = 0.8); and 46%, 44%, and 35% (p = 0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. Conclusions Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.

scholarly journals The Colony-Stimulating Factor 3 Receptor M696T Mutated in a Patient with Ph+ Acute Lymphoblastic Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Xin Chen ◽  
Bichen Wang ◽  
Aiming Pang ◽  
Erlie Jiang ◽  
Yajing Chu ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Myelogenous Leukemia ◽  
Unrelated Donor ◽  
Colony Stimulating Factor ◽  
Term Survival ◽  
Long Term Survival ◽  
Tumor Transformation ◽  
Stimulating Factor

Purpose: Colony-stimulating factor 3 receptor (CSF3R) mutations have been identified in a variety of myeloid disorders, such as severe congenital neutropenia (SCN), chronic neutrophilic leukemia (CNL), myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and atypical chronic myelogenous leukemia (aCML). Although CSF3R point mutations (e.g., T618I) are emerging as key players in CNL/aCML, the significance of rarer CSF3R mutations is unknown. We report a case of philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) with the M696T mutation in CSF3R gene and assess the pathogenicity of the CSF3R M696T mutation in Ph+ ALL. Experimental Design: Here we report on a 32-year-old female who presented with asthenia. The initial hematological workup revealed white blood cell (WBC) count of 97 x 109/L (normal range 4-10 x 109/L). There was 84% prolymphocyte in the bone marrow. The immunophenotype of the blasts as judged from flow cytometry was in accordance with a B-ALL. The fusion gene for BCR-ABL P210 was positive. Hot mutation closely related to diseases was: CSF3R (nucleotide change c.2087 T&gt;C, amino acid change p.M696T, mutation frequency 50.4%). Cytogenetic analysis showed 46, XX, t (9;22) (q34;q11). The patient was diagnosed as Ph+ ALL with the CSF3R M696T mutation and achieved Long-term survival after unrelated donor hematopoietic stem cell transplantation. Meanwhile we performed a series of experiments using murine interleukin 3 (IL-3)-dependent Ba/F3 cell line to evaluate the transforming capacity of the CSF3R M696T mutation. The phosphorylation of STAT3 was analyzed by G-CSF dependence assays and immunoblot analysis to evaluate the CSF3R M696T mutation contribution to the tumor transformation ability of Ba/F3 cells. Results: This patient achieved complete remission with chemotherapy in combination with tyrosine kinase inhibitor (TKI) and long-term survival by unrelated donor transplantation. We confirmed the presence of a CSF3R M696T germline mutation in this patient, and the mutation was inherited from her mother. The experiments in vitro result showed the CSF3R M696T mutation harbors marginal contribution to the tumor transformation ability of Ba/F3 cells. CSF3R M696T mutation was neutral in tumor transformation ability. Conclusions: We believe that TKI is still effective in patients with the CSF3R M696T mutation in Ph+ ALL. Donor with CSF3R M696T mutation might still be selected. Disclosures No relevant conflicts of interest to declare.

scholarly journals Marrow Transplants From Unrelated Donors for Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1410-1414 ◽  
Author(s):  
Jorge Sierra ◽  
Jerry Radich ◽  
John A. Hansen ◽  
Paul J. Martin ◽  
Effie W. Petersdorf ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Early Stage ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Unrelated Donor ◽  
Effective Treatment Option ◽  
Patients At Risk ◽  
Unrelated Donors ◽  
First Relapse ◽  
Philadelphia Chromosome Positive

Transplantation of marrow from unrelated donors was investigated in patients with Philadelphia chromosome-positive (Ph1+) acute lymphoblastic leukemia (ALL) who lacked a suitable family donor. Eighteen patients underwent transplantation at our center between 1988 and 1995. The median patient age was 25 years (range, 1.7 to 51 years). Seven patients were in first complete remission, 1 in second remission, 3 in first relapse, and the remaining 7 had more advanced or chemotherapy refractory leukemia at transplant. All patients were conditioned with cyclophosphamide and total body irradiation followed by marrow transplants from closely HLA-matched, unrelated volunteers. Posttransplant graft-versus-host disease (GVHD) prophylaxis included methotrexate with either cyclosporine or FK506. Graft failure was not observed. Severe (grades III-IV) GVHD appeared in 6 of 17 evaluable patients and chronic extensive GVHD in 7 of 13 patients at risk. Five patients had recurrent ALL after transplantation and another 4 died from causes other than leukemia. Six patients transplanted in first remission, 2 in first relapse, and 1 in second remission remain alive and leukemia-free at a median follow-up of 17 months (range, 9 to 73 months). The probability of leukemia-free survival at 2 years is 49% ± 12%. These data indicate that unrelated donor marrow transplantation is an effective treatment option for patients with early stage Ph1+ ALL without a family match and suggest that in such patients an unrelated donor search should be initiated as soon as possible after diagnosis.

HLA Haploidentical versus Matched Unrelated Donor Transplants with Post-Transplant Cyclophosphamide based prophylaxis

Blood ◽  
2021 ◽  
Author(s):  
Mahasweta Gooptu ◽  
Rizwan Romee ◽  
Andrew St. Martin ◽  
Mukta Arora ◽  
Monzr M. Al Malki ◽  
...  
Keyword(s):  
Overall Survival ◽  
Graft Failure ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Conditioning Regimens ◽  
Disease Free ◽  
Reduced Intensity ◽  
Grade Iii

Post transplant cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis has allowed haploidentical (Haplo) transplantation to be performed with results similar to that after matched unrelated donor (MUD) transplantation with traditional prophylaxis. The relative value of transplantation with MUD versus Haplo donors when both groups receive PTCy/calcineurin inhibitor/mycophenolate containing GVHD prophylaxis is not known. We compared outcomes after 2036 Haplo and 284 MUD transplantations with PTCy GVHD prophylaxis for acute leukemia or myelodysplastic syndrome in adults between 2011 and 2018. Cox regression models were built to compare outcomes between donor types. Recipients of myeloablative and reduced intensity regimens were analyzed separately. Among recipients of reduced intensity regimens, 2-year graft failure (3% versus 11%), acute grade II-IV GVHD (HR 0.70, p=0.022), acute grade III-IV GVHD (HR 0.41, p=0.016) and non-relapse mortality (HR 0.43, p=0.0008) were lower after MUD compared to Haplo transplantation. Consequently, disease-free (HR 0.74, p=0.008; 55% versus 41%) and overall survival (HR 0.65, p=0.001; 67% versus 54%) were higher after MUD compared to Haplo transplants. Among recipients of myeloablative regimens, day-100 platelet recovery (95% versus 88%) was higher and grade III-IV acute (HR 0.39, p=0.07) and chronic GVHD (HR 0.66, p=0.05) were lower after MUD compared to Haplo transplantation. There were no differences in graft failure, relapse, non-relapse mortality, disease-free and overall survival between donor types with myeloablative conditioning regimens. These data extend and confirm the importance of donor-recipient HLA matching for allogeneic transplantation. A MUD is the preferred donor, especially for transplantations with reduced intensity conditioning regimens.

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