The long-term outcome of reduced-intensity allogeneic stem cell transplantation from a matched related or unrelated donor, or haploidentical family donor in patients with leukemia: a retrospective analysis of data from the China RIC Cooperative Group

Abstract

This study compared 6-year follow-up data from patients undergoing reduced-intensity conditioning (RIC) transplantation with an HLA-matched related donor (MRD), an HLA-matched unrelated donor (MUD), or an HLA-haploidentical donor (HID) for leukemia. Four hundred and twenty-seven patients from the China RIC Cooperative Group were enrolled, including 301 in the MRD, 79 in the HID, and 47 in the MUD groups. The conditioning regimen involved fludarabine combined with anti-lymphocyte globulin and cyclophosphamide. Graft-versus-host disease (GVHD) prophylaxis was administered using cyclosporin A (CsA) and mycophenolate mofetil (MMF). Four hundred and nineteen patients achieved stable donor chimerism. The incidence of stage II-IV acute GVHD in the HID group was 44.3 %, significantly higher than that in the MRD (23.6 %) and MUD (19.1 %) groups. The 1-year transplantation-related mortality (TRM) rates were 44.3, 17.6, and 21.3, respectively. Event-free survival (EFS) at 6 years in the HID group was 36.7 %, significantly lower than that of the MRD and MUD groups (59.1 and 66.0 %, P < 0.001 and P = 0.001, respectively). For advanced leukemia, the relapse rate of the HID group was 18.5 %, lower than that of the MRD group (37.5 %, P = 0.05), but the EFS at 6 years was 31.7 and 30.4 % (P > 0.05), respectively. RIC transplantation with MRD and MUD had similar outcome in leukemia which is better than that with HID. RIC transplantation with HID had lower relapsed with higher TRM and GVHD rate, particularly in advanced leukemias. RIC transplantation with MRD and MUD had similar outcomes in leukemia and they were better than those with HID. RIC transplantation with HID had a lower relapse rate but higher TRM and GVHD rates, particularly in cases of advanced leukemia.

The consensus on indications, conditioning regimen, and donor selection of allogeneic hematopoietic cell transplantation for hematological diseases in China—recommendations from the Chinese Society of Hematology

“…Select older patients (age > 50) with low HCT-CI (<= 2) and good performance status tolerated myeloablative haplo-HSCT with similar outcomes as younger adults [ 57 ]. Haplo-HSCT with a reduced-intensity regimen (RIC) with substitution of cyclophosphamide with fludarabine (Flu) was feasible in patients above 60 years of age, who exhibited similar engraftment and relapse rates as myeloablative conditioning in China [ 29 , 30 ]. Select adults ≥ 70 years with hematological malignancies are considered for transplant in the USA.…”

Tumorablative conditioning regimen for haploidentical stem cell transplantation in 102 children with hematologic malignancies: a single-center experience

“…The cumulative incidence rates of II-IV GVHD and severe GVHD were 29.3% and 9%, respectively, it was no increase in incidence compared with literature. 2-year cumulative relapse rate (CR = 17.4%, NR+PR = 13.3%) and a 2- year TRM of 4.9% were maintained at a relatively low level compared with previously published literature on haploid transplantation [ 25 , 26 ]. The results showed that the recurrence was markedly reduced and the tolerance was good in haplo-HSCT.…”

Effective T‐cell replete haploidentical stem cell transplantation for pediatric patients with high‐risk hematologic disorders

“…First, the ex vivo depletion of T‐cells, which is accomplished using several techniques to reduce donor T‐cell counts in stem cell products, such as the selection of CD34+ cells, depletion of CD3+ and CD19+ cells, and depletion of αβTCR+ cells, is commonly performed in Europe 7–10 . Second, the GIAC protocol, which is based on a granulocyte colony‐stimulating factor to stimulate the donor's progenitor cell production, together with intensified immunosuppression (cyclosporine, mycophenolate mofetil, and short‐course methotrexate), anti‐thymocyte globulin to facilitate conditioning, and a combination of peripheral blood stem cell and bone marrow allografts, has been extensively used in China 11–13 . Lastly, in vivo depletion of alloreactive T cells, accomplished with high‐dose cyclophosphamide after unmanipulated stem cells were given to patients, was pioneered in the United States 14–16 …”