Tumorablative Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of High-Risk and Refractory Leukemia — New Concepts and Clinical Practice

Abstract

The substance of bone marrow transplantation is the organ transplantation. "ccurately, it is the grafting of hematopoietic and immunologic system. Comparing to the transplantation of solid organ, in the hematopoietic stem cell transplantation HSCT , the ill organ, id est. hematopoietic and immunology system, is ablated by high-dose chemotherapy and total body irradiation T"I conditioning regime . Thus, the normal hematopoietic stem cells could be engrafted and normal function of hematopoietic and immune system could be reconstituted. The standard myeloablative conditioning regimen would be reasonable or enough for the non-malignances of marrow, which needed by replacing therapy, such as marrow failure. However, for treatment of hematopoietic malignances, it maybe not cure the malignance diseases to ablate the normal hematopoietic, immune system and reconstitute the normal function of allogeneic hematopoietic and immune system of patients. "ecause the leukemic stem cells LSC are not only existence in the bone marrow, it might be occurrence in any site of body. For instance, the traditional myeloablative conditioning regimen to treat leukemia could have striking killing effects of leukemic cells, and residual leukemic cells further eradicated by effect of the graft versus leukemia GVL , but the malignant cells are not always removed at all in the all patients, therefore, relapse post transplantation could be occurred in the some patients. In fact, the traditional allogeneic myeloablative HSCT could cure or improve outcome of acute leukemic patients with standard risk, however, the disease relapse after transplant for acute leukemia with high risk and refractory is % to % [ -]. Moreover, the leukemic cells in the majority of relapsed cases originate from inceptive

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

“…Therefore, it is of great importance to seek a novel conditioning regimen to eliminate the leukemia as much as possible without increasing the TRM. According to the concept of tumorablative hematopoietic stem cell transplantation published previously [ 5 , 6 ], in this paper, we designed a TAC combined haplo-HSCT for children with hematologic malignancies in our center.…”

Tumorablative haploidentical hematopoietic cell transplantation for treatment of hematologic malignancy in children

“…The preliminary results have demonstrated that it reduced the relapse to about 20% in these patients. 4,5 Here we report the results of using TAHCT to treat the children patients with high-risk or relapsed hematologic malignancies.…”

“…The further regimen was based on our previous protocol for adult HSCT. 5 Briefly, two regimens were included: regimen A, for patients who were older than 3 years or with extramedullary involvement: X (which is the effective anthracycline sought from the patient's chemotherapy history, for example, idarubicin 10 mg/m 2 .d, or aclarubicin 0.8 mg/kg.d, or mitoxantrone 10 mg/m 2 .d) (day − 14 to − 12), fludarabine 40 mg/m 2 .day (day − 13 to − 9), Ara-C 0.5-2.0 g/m 2 .12 h (day − 13 to − 9), rhG-CSF 5 ug/kg.day (day − 14 to − 9), teniposide (VM-26) 300 mg/m 2 .day (day − 8), TBI with 4.5 Gy/day (days − 7 to − 6), CY 40 mg/kg.day (days − 5 to − 4) and rabbit ATG (Fresenius) 5 mg/kg.day (days − 5 to − 2). The day of bone marrow (BM) and PBSC infusion was designated as day 1 and day 2.…”

“…We have previously pioneered the new concept of TAHCT for treatment of those patients with high-risk, refractory, even advanced-stage acute leukemia. 5 The TAHCT involve all parts in procedure of transplantation, the principal contents include individual tumorablative conditioning regimen and enhancing the immunotherapy post transplantation. 5 Here we used the further tumorablative regimen to treat the 26 children with high-risk or relapsed hematologic malignancies.…”

“…5 The TAHCT involve all parts in procedure of transplantation, the principal contents include individual tumorablative conditioning regimen and enhancing the immunotherapy post transplantation. 5 Here we used the further tumorablative regimen to treat the 26 children with high-risk or relapsed hematologic malignancies. In the median follow-up of 20.1 months, 1 year OS and DFS was 84.6% and 80.8%, respectively, only two patients experienced relapse after grafting.…”