Clinical Study on Patients with Advanced Malignant Hematopoietic Disease by Non-T Cell Depleted Haploidentical Hematopoietic Stem Cells Transplantation.

objective: To investigate the effect of non-T cell depleted HLA haploidentical bone marrow transplantation(BMT) to patients with advanced malignant hematologic disease.

Method: 26 patients with advanced malignant hematologic disease received non-T cell depleted haploidentic BMT. Donors included group A: offspring(5cases), sibling(3cases) and group B: mother(18cases). Hematologic Stem Cells(HSC) mobilization, collection and infusion: donors received G-CSF(300ug/12h×15d) from −5d, bone marrow cells were collected at −2d, PBSC were collected at −1d if CD34+ cells less than 4×10⁶/kg of recipient’s body weight. The average of CD34+ cells were 5.91(3.66~9.29) ×10⁶/kg of recipient’s body weight, the average of MNC were 10.05(2.10~29.70) ×10⁸/kg of recipient’s body weight. Preparative regimens: recipients were prepared for transplantation with different conditioning regimens according to the type of disease. Myeloid leukemia regimen: MeCCNU 250mg/m² −10d, Ara-C 2g/m² q12h, from −9d to −8d, Bu 4mg/kg, from −7d to −5d, Cy 1.8g/m².d, from −4d to −3d. Lymphoblastic leukemia regimen: MeCCNU 250mg/m² −8d, Total-body irradiation(TBI) 8Gy −7d, Ara-C 2g/m² q12h, from −6d to −5d, Cy 1.8g/m².d, from −4d to −3d. All the patients were given hydration, alkalization, and given mesna to prevent hemorrhage cystitis. GVHD prophylaxis: All patients received GVHD prophylaxis consisting of Cyclosporine(CSA), Methotrexate(MTX), Mycophenolate mofetil(MMF) and antithymocyle globulin(ATG). When GVHD developed, methylprednisolone(MP) was given at first, if the response was poor, anti-CD25 antibody was given to the recipients as quickly as possible and CSA was replaced with tacrolimus.

[Results] All patients achieved sustained, full-donor-type engraftment. CD34+ cells in graft were (5.91±1.34)×10⁶/kg of recipient’s body weight, all patients attained successful neutrophil recovery at a median of (12.2±2.82) days (range, 10 to 20 days), recovery of platelet counts of more than 20×10⁹/L was observed at a median of (20.73±7.62) days (range, 13 to 44 days). All the patients detected 99.9%~100% donor chimerism with FISH, recipient blood type of red blood cells transferred to donor blood type, STR showed donor chimerism exceeded 93%. 23 patients developed aGVHD in 26, the respective number of patients who developed grade I, II, III or IV aGVHD was 7, 7, 2, 7, the cumulative incidence of grade II–IV aGVHD was 65.4% and grade III–IV aGVHD was 34.6%. 12 patients developed cGVHD, the incidence was 46.2%. As of July 30 2005, 10 patients died, owing to pulmonary infection in 7, septicemia and HC in 1, leukoencephalopathy in 1, and recurrent disease in 1 case. 16 patients were alive and disease free with 2 years disease-free survival probabilities of 49.04%, 6 patients died in group A with 1 year disease-free survival probabilities of 25%, 4 patients died in group B with 2 years disease-free survival probabilities of 62.5%, p=0.0012 with Log-Rank test

Conclusion HLA-haploidentical BMT is a effective treatment for advanced malignant hematologic disease. Donor from mother is superior to the donor from sibling and offspring with lower aGVHD incidence, lower mortality and longer survival.