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.

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.

[Multicenter report of nonmyeloablative allogeneic stem cell transplantation for hematologic diseases].

OBJECTIVE: To observe the treatment effect and toxicity of nonmyeloablative allogeneic stem cell transplantation (NST) for hematologic diseases. METHODS: A total of 243 hematologic diseases patients received HLA-identical NST were enrolled in this study from 9 transplant centers of NST Cooperative Group in China. Nonmyeloablative conditioning regimen was based on fludarabine (Flud), rabbit anti-human thymocyte globulin (ATG), cyclophosphamide (CTX) (FAC), and plus cytarabine or busulfan (BU) etc. Graft-versus-host disease (GVHD) prophylaxis included cyclosporin A (CsA) and mycophenolate mofetil (MMF). RESULTS: Among the 243 patients, 219 (90.1%) achieved full donor chimerism (FDC), 2(0.8%) engraftment failure. 78 (32.1%) had mixture chimerism (MC) at 4 weeks after NST, out of which 56 switched to FDC, 16 remained MC and 6 (2.5%) developed graft rejection. The incidence of acute GVHD was 34.2%, including 6.6% of grade III-IV acute GVHD. Chronic GVHD developed in 78 (32.1%) patients. The follow-up durations were 3 - 99 months, 162 (66.7%) were still alive and the overall survival rates were 76.5%, 73.9%, 70.7%, and 27.8% for MDS/SAA, chronic myeloid leukemia, acute leukemia at first remission, and refractory or relapsed leukemia, respectively. CONCLUSIONS: The nonmyeloablative allogeneic stem cell transplantation based on FAC conditioning results in sustained engraftment and mild aGVHD, providing a new feasible curative therapy for hematology diseases.

[Comparison of conditioning regimens containing or no fludarabine in nonmyeloablative allogeneic peripheral blood stem cell transplantation].

OBJECTIVE: To investigate the therapeutic effect of conditioning regimen containing fludarabine in nonmyeloablative allogeneic peripheral blood stem cells transplantation (NAST) in the treatment of hematological diseases. METHODS: Thirty-six patients with acute leukaemia, severe aplastic anaemia, MDS and myelofibrosis received NAST from HLA matched donors' G-CSF mobilized peripheral blood stem cells after nonmyeloabalative conditioning. The conditioning regimen consisted of CTX, Ara-C, CsA, anti-CD(3) antibody or anti-thymocyte globulin and with or without fludarabine. GVHD prophylaxis was performed with cyclosporine combined methotrexate (no MMF group, n = 5) or mycophenolate mofetil (MMF group, n = 31). RESULTS: All of the treatment was generally well tolerated and all cases achieved engrafted of the donor cells. In fludarabine group, engraftment was observed in 87.5% (14/16) patients with complete donor chimerism, graft failure was 12.5% (2/16) and in no fludarabine group, 80% (16/20) and 20% (4/20), respectively. The incidence of acute GVHD (grade I - IV) was 27.8% (10/36) and chronic GVHD 22.2% (8/36). In fludarabine group, grade I - II aGVHD was 37.5%, in no fludarabine group, 20%. cGVHD was 12.5% in fludarabine group and in no fludarabine group 30%, respectively. Interstitial pneumonia (IP) was observed in 16.7% (6/36) of the patients, being 18.7% (3/16) and 15% (3/20) in fludarabine and no fludarabine group, respectively. Overall survival rate was 80.5% (29/36) with a median follow-up of 13 months. CONCLUSIONS: There was no significant difference between fludarabine based (n = 16) and non-fludarabine based conditioning regimen (n = 20) in NAST for the treatment of hematological diseases, regarding for incidence of GVHD, IP, engraftment and survival.

[Clinical significance of formation and conversion of hematopoietic mixed chimerism in nonmyeloablative allogeneic stem cell transplantation].

OBJECTIVE: To study the clinical significance of formation and conversion of hematopoietic mixed chimerism in nonmyeloablative allogeneic hematopoietic stem cell transplantation (NAST) in treatment of hematological diseases. METHODS: Nonmyeloablative pretreatment was given to 42 patients with hematological diseases, 26 males and 16 females with the median age of 37, that were matched with the donors in terms of HLA, such as CD3 monoclonal antibody, cyclosporine A, cyclophosphamide (CTX) and cytarabine for patients with leukemia among which 6 were given fludarabine in addition, and CTX and antilymphocyte globulin for patients with myeloproliferative disease and aplastic anemia, thus practicing nonmyeloablative allogeneic stem cell transplantation (NAST). The incidence of graft-versus-host disease (GVHD) and survival were observed. RESULTS: Donor-recipient hematopoietic cell chimerism was formed in 42 patients, with 18 cases of full donor chimerism (FDC) and 24 cases of mixed chimerism (MC). Of the 42 patients, 10 (23.8%) developed acute GVHD (aGVHD). The incidence of aGVHD in group MC (2/24, 8.9%) was significantly lower than that in group FDC (8/24, 44.4%, P < 0.05). In addition, eight (19.1%) developed chronic GVHD (cGVHD). The incidence of cGVHD was also lower in group MC (4/24, 16.7%) in comparison with 4/18 (23.2%) in group FDC (P > 0.05). There was no difference in recovery time of neutrophils and platelets (P > 0.05) between the two groups. Thirty-one patients still survived and there was no significant difference between the group FDC and MC in terms of survival rate and leukemia relapse rate. CONCLUSION: Compared with full donor chimerism, mixed chimerism significantly alleviates the incidence of aGVHD and does not delay the hematopoietic reconstitution. It may be an ideal model of engraftment that mixed chimerism converts to full donor chimerism within several months after NAST.

[The clinical research of nonmyeloablative allogeneic peripheral blood hematopoietic stem cells transplantation for hematological diseases].

OBJECTIVE: To explore the significance of nonmyeloablative allogeneic peripheral blood hematopoietic stem cell transplantation in the treatment of hematological diseases. METHODS: A nonmyeloablative conditioning regimen consisted of CD(3) monoclonal antibody, cyclosporine A, cyclophosphamide and cytarabine was used for allogeneic stem cell transplantation in 33 patients with hematological diseases. Of them, 11 were acute leukemia (AL) in first complete remission (CR(1)), 4 AL-CR(2) approximately 3, 3 refractory AL, 4 severe aplastic anemia (SAA), 7 chronic myeloid leukemia (CML), 2 myelodysplastic syndrome, 1 each of chronic lymphocytic leukemia (CLL) and myelofibrosis. RESULTS: All 33 patients passed the hematopoietic suppression stage smoothly and achieved engraftment of the donor cells. There were 24 cases of full donor chimerism (13 cases converted from mixed chimerism), 4 mixed chimerism (MC) and 5 developed graft rejection. Of the 33 cases, 7 (21.2%) developed acute GVHD and chronic GVHD, 25 (75.8%) still live and 8 (24.2%) died. CONCLUSIONS: Nonmyeloablative allogeneic peripheral blood stem cells transplantation is a safe, less toxic and curative approach for patients with hematological disease.

[Significance of serological test of blood group in nonmyeloablative allogeneic peripheral blood stem cell transplantation of patients with acute leukemia].

The purpose of this study is to explore the clinical significance of RBC blood group serological test in nonmyeloablative allogeneic peripheral blood stem cell transplantation (NAPBSCT) of ABO group incompatibility in 4 patients with acute leukemia. ABO and MN blood group of donors and recipients were determined by hemagglutination test and Rh blood group by Diana Gel phenotype Rh card. The changes of blood group in recipients were observed and implant of donor cells was monitored by short tandem repeat-PCR method. The results showed that in 2 cases of 4 recipients the marrow cells appeared mixed chimera of donor and recipient cells, and blood group changed to donor type in 1 of the 2 cases on 100 days after transplantation. In another 2 cases, the marrow cells appeared mixed chimera without blood group chimera on 154 days after transplantation, and rejection of the transplant occurred in 1 of the 2 cases. The determination of hemagglutinin titer showed that the implant rate of donor cells was lower in the recipients with higher hemagglutinin titer and blood group chimera did not appear, conversely, the implant rate was higher in the recipients with lower titer and blood group chimera appeared early. It is concluded that examination of RBC blood group in NAPB SCT can indirectly reflect effectiveness of transplantation, contribute to decide the intensity of conditioning protocol and immunosuppressive therapy after transplantation, estimate prognosis and guide blood transfusion during transplantation.