HLA-Haploidentical Related Hematopoietic Stem Cell Transplantation and Mesenchymal Stem Cell Transplantation in Patients with Hematologic Malignancies.

Abstract

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only way to cure many hematologic malignancies. HLA-haploidentical related HSCT was performed in case of lack of HLA-matched donors. From the results of in-vitro and animal studies, Mesenchymal stem cells (MSCs) transplanted simultaneously with hematopoietic stem cells (HSCs) may support hematopoietic regeneration and have the immunomodulatory effect. MSCs together with HSCs transplantation from the same HLA-haploidentical donor were used in patients with hematologic malignancies.Patients and Methods: Three patients were chronic myeloid leukemia (blast crisis), chronic myeloid leukemia (chronic phase) and refractory T-cell lymphoblastic lymphoma (leukemia phase) respectively. Complete demographic and clinical details of these 3 patients are shown in Table 1. Bone marrow mononuclear cells obtained from their HLA-haploidentical related donors were cultured and expanded in vitro about 2 months before transplantation. Immunophenotype of the harvested cells were detected in order to identify them. After conditioned by cytosine arabinoside/cyclophosphamide/total body irradiation regimen, patients were co-transplanted with HSCs and ex-vivo expanded MSCs. Cyclosporine, methotrexate, antithymocyte globulin, mycophenolate mofetil and anti-CD25 monoclonal antibody were used together for prophylaxis of GVHD. Clinical features after transplantation in these patients were observed.Results: About 2×106 MSCs per kilogram of recipients' weight were successfully expanded from bone marrow samples. These cells were CD73, CD90, CD105 positive and CD34, CD45, CD38, CD10, CD20, CD33, HLA-DR negative by flow cytometric analysis. No adverse response was observed during and after infusion of MSCs. Hematopoietic reconstruction was successful in all the patients. And they had full donor-type chimerism 1 month after transplantation. N1 received donor lymphocyte infusion (DLI) to prevent the relapse. N2 relapsed and received the therapy of STI571 combined with DLI. She had a complete remission at last. No graft-versus-host disease (GVHD) was observed in N1 and N2 until they received DLI. N1 died of infection 11 months after transplantation. N2 and N3 now have been followed up for 41 and 31 months respectively. Clinical features of patients after transplantation are shown in Table 2.Conclusions: Bone marrow derived MSCs can be tolerant well in HLA-haploidentical HSCT. Its exact effect in human HLA-haploidentical allogeneic HSCT needs to be studied further.Tab.1Patient Demographic and Clinical DataPatientDiagnosisAgeSexCourse of disease before transplantationDonorMismatched HLA lociN1T-LPL22F7 yrmother3N2CML-BC32F6mosibling brother3N3CML-CP22M5mofather3Abbr: LPL - lymphoblastic lymphoma; CML - chronic myeloid leukemia; BC - blast crisis; CP - chronic phase; yr - year; mo - monthTab.2Clinical features of patients after transplantationPatientHematopoietic reconstructionDonor-type chimerismTime of relapsetime of DLIacute GVHDchronic GVHDsurvivalN115 d100%no5 moIV (after DLI)extensivedie in 11 moN216 d100%6mo6 moIV (after DLI)no>41 moN315 d100%nonoIlimited>31 moAbbr: DLI - donor lymphocyte infusion; d - day; mo - month