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Objective@#To analyze the efficacy of HLA-haploidentical peripheral hematopoietic stem cell transplantation (haplo-PBSCT) following reduced intensity conditioning (RIC) regimen to treat the patients with hematological malignancies who were older than 50 years old.@*Methods@#Eighteen patients with hematological malignancies over 50 years were enrolled, including 8 male and 10 female patients. The median age of all patients was 52 (range: 50–66) years. Of them, 8 patients had acute myeloid leukemia (AML) , 2 chronic myelocytic leukemia (CML) , 5 myelodysplastic syndrome (MDS) , 2 acute lymphoblastic leukemia (ALL) , and 1 aggressive natural killer cell leukemia (ANKL) . All patients received fludarabine, cytarabine and melphalan with rabbit anti-human thymocyte globulin (FAB+rATG regimen) and transplanted with high dose non-T cell-depleted peripheral hematopoietic stem cells from donors. Enhanced graft versus host disease (GVHD) prophylaxis and infection prevention were administered.@*Results@#Fifteen days after transplantation, 16 patients achieved complete donor chimerism. One of them rejected the donor graft completely at thirty days after transplantation, and the other 2 patients had mixed chimerism 15 days after transplantation and converted to complete recipient chimerism at 30 days after transplantation. The cumulative incidence of acute GVHD (aGVHD) was 61.1% (95%CI49.6%-72.6%) . The incidence of grade Ⅱ-Ⅳ aGVHD was 35.4% (95%CI 21.1%-49.7%) , whereas grade III-IV was 13.8% (95%CI 4.7%-22.9%) . The 2-year cumulative incidence of chronic GVHD (cGVHD) rate was estimated at 38.2% (95%CI 25.5%-50.9%) . Patients were followed-up for a median of 14.5 months (range, 3-44 months) . The Kaplan Meier estimates of 2-year overall survival (OS) and disease-free survival (DFS) was 72.6% (95%CI 60.1%-85.1%) and 63.7% (95%CI 49.2%-78.2%) , respectively. The 2-year cumulative incidence of relapse and non-relapse-mortality (NRM) was 31.2% (95%CI 16.5%-45.9%) and 12.5% (95%CI 4.2%-20.8%) , respectively.@*Conclusion@#RIC-haplo-PBSCT protocol can achieve better results in patients with hematologic malignancies over 50 years old.
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Objective To explore the clinical outcome of HLA haploidentical vs HLA-matcbed peripheral blood hematopoietic stem cell transplantation (PBSCT) without in vitro T-cell depletion for malignant hematological diseases. Methods 111 patients with malignant hematological diseases underwent PBSCT without in vitro T-cell depletion between May 2004 and February 2009, including 51 patients with HLA-haploidentical and 60 patients with HLA-matched. All patients have received myeloablative conditioning regimen. A two-agent based graft-versus-host disease (GVHD) prophylaxis was used as cyclosporine A and a short course of methotrexate. Mycophenolate mofetile was added for the patients with one locus mismatch. Mycophenolate mofetile, antithymocyte globulin and CD25 monoclonal antibody were added for the patients with 2-3 loci mismatch. The grafts were granulocyte colony-stimulating factor-mobilized peripheral blood stem cells without in vitro T-cell depletion. Results 111 patients achieved sustained and full donor-type engraftment. The median time to reach an absolute neutrophil count above 0.5×10~9/L was 14 days and that to a platelet count exceeding 20×10~9/L was 15 days in 51 HLA-haploidentical patients, and that was 12 days and 13 days in 60 HLA-matched patients, respectively. In 51 HLA-haploidentical patients, 25 patients developed aGVHD, including 20 cases of grade Ⅰ aGVHD, and 5 cases of grade Ⅱ. Thirty-three patients developed cGVHD with limited in 30 and extensive in 3. The 4-year cumulative incidence of cGVHD was 70.4 %. The 3-year probabilities of leukemia-free survival (LFS) were 74.5% (77.3 % for standard risk patients and 68.2 % for high risk patients respectively). Seven patients had recurrence. In 60 HLA-matched patients, 14 patients developed aGVHD, including 10 cases of grade Ⅰ, 2 cases of grade Ⅱ and 2 cases of grade Ⅲ. Thirty-seven patients developed cGVHD with limited in 32 and extensive in 5. The 4-year cumulative incidence of cGVHD was 58.1%. The 3-year probabilities of LFS were 72.1% (77.6 % for standard risk patients and 52.7 % for high risk patients respectively). Ten patients had recurrence. The incidence of aGVHD in HLA-haploidentical cohort was significantly higher than in HLA-matched cohort (P<0.05). There was no significant difference in incidence of cGVHD, incidence of relapse and LFS between HLA-haploidentical and HLA-matched cohorts (P>0.05). Conclusion Haploidentical PBSCT is feasible and safe for malignant hematological diseases to use myeloablative conditioning regimen in combination with intensive immunosuppressants without in vitro T cell depletion.
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BACKGROUND: Lack of human leucocyte antigen-matched family donors has restricted the application of hematopoietic cell transplantation. Due to immunological disorder of humam leucocyte antigen misfit, common way for haploidentical transplantation is associated with poor engraftment and severe graft-versus-host disease. Because not every patient has HLA-Jdentical family member, a substantial proportion of patients will receive haploidentical transplantation. OBJECTIVE: To explore the curative effect on malignant hematological diseases of haploidentical peripheral blood stem cell transplantation (PBSCT) using myeloablative conditioning regimen in combination of proper immunosuppressants without in vitro T-cell depletion. DESIGN, TIME AND SETTING: A case observation was performed at the Department of Hematology in the First Affiliated Hospital of Xinjiang Medical University from July 2002 to June 2008. PARTICIPANTS: Forty-two patients with malignant hematological diseases, including 29 standard-risk patients and 13 high-risk patients, age from 10 to 48 years, were transplanted with cells from a haploidentical family donor with 1-3 mismatched loci of HLA antigens. Seven patients had 1 locus mismatched donors and thirty-five patients had 2-3 loci mismatched donors. METHODS: The patients have received myeloablative conditioning regimen. A two-agent based graft-versus-host disease (GVHD) prophylaxis was used as cyclospodne A and a short course of methotrexate. Mycophenolate mofetile was added for 1 locus mismatched patients. Mycophenolate mofetile, antithymocyte globulin and CD25 mono-colonal antibody were added for 2-3 loci mismatched patients. The grafts were granulocyte colony-stimulating factor-mobilized peripheral blood stem cells without in vitro T-cell depletion. MAIN OUTCOME MEASURES: Engraftment, GVHD incidence and severity, relapse and leukemia-free survival and the immune function of patients in months 1, 3, 6, 12 and 18 postoperatively. RESULTS: Totally 42 patients achieved complete and sustained donor-type engraftment. Nineteen patients developed acute GVHD, the 2-year cumulative incidences of acute GVHD were 50.8%, gradeⅠ acute GVHD occurred in 16 cases and grade Ⅱ in 3 cases. Thirty-one patients were followed up more than 6 months, 23 of them developed chronic GVHD with limited in 20 and extensive in 3, the 2-year cumulative incidences of chronic GVHD were 57.1%. No patients died of GVHD. There were no significant differences in the reduction and recovery of T cells and B cells between HLA haploidentical PBSCT without in vitro T cell depletion and HLA-matched PBSCT. CONCLUSION: Haploidentical PBSCT is feasible and safe for malignant hematological diseases to use myeloablative conditioning regiment combination of intensive immunosuppressants without in vitro T cell depletion. A large amount of clinical cases need to be investigated in the near future.
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Objective To investigate the correlation between immature granulocyte and CD34+ cells, mononuclear cells (MNC) in donor's peripheral blood by recombinant human granulocyte colony-stimulating factor (rhG-CSF). Methods The stem cell were mobilized by rhG-CSF 7.25-10 μg·kg-1·d-1 from 122 allo-PBSCT donors. Before and after mobilization, to test CD34+ cells of peripheral blood stem cell graft and number of MNC, immature granulocyte, CD34+ cell per patient' weight were calculated. Results White blood cell count and immature granulocyte gradually increased, and reached the peak on the frith day. There was a good relationship between increased immature granulocytes and increased CD34+ cells. The patients all achieved completed donor engraftment and achieved hematopoietic recovery. The chromosome, blood type and HLA type were transformed to be donor's type. Ph1 changed to be negative in CML patients. Conclusion rhG-CSF (7.25～10 μg·kg-1·d-1) had a good effect to mobilize PBSC. There was a good relationship between in-creased immature granulocytes and increased CD34+ cells after mobilization by rhG-CSF. The number of immature granulocytes can reflect indirectly the count of stem/progenitor, so the MNC and immature granulo-cytes can become a threshold of dosage standard.