“Back-up” Stem Cell Harvest Is Beneficial for Patients Receiving Unrelated Donor Allogeneic Hematopoietic Cell Transplantation.

Abstract 4524

Graft failure or graft rejection is a serious and potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT), which occurs at an overall frequency of less than 5%. Before 2005, in our unit we tried to manage this complication by infusion of hematopoietic stem cells (HSCs) from an alternative donor (n=2) or cord blood (n=2). Unfortunately, these 4 patients could not achieve neutrophil engraftment and died of serious infections. Thus, in case of engrafment failure, donor reneging or other unpredictable conditions, we have advised the storage of “back-up” cells for all patients undergoing unrelated allo-HSCT since 2005. Before allo-HSCT, patients with chronic myelogenous leukemia (CML) mobilized with G-CSF after intravenous cyclophosphamide 2g/m² for 2 days, whereas patients with other acute leukemia mobilized with G-CSF during the agranulocytosis phase after chemotherapy. “Back-up” cells were harvested as soon as white blood cell count was greater than 2×10⁹/L, and cryopreserved in liquid nitrogen. From Jan 2005 to Dec 2009, 118 patients stored autologous “backup” cells, among whom 19 CML patients underwent fludarabine based reduced intensity conditioning regimen, and other patients underwent BuCy based myeloablative conditioning regimen. All patients underwent non-manipulated marrow or peripheral stem cell transplantation. None of these 118 patients developed harvest- related- complication when “back-up” cell mobilization and harvest. The medial mononuclear cells (MNC) count in “back-up” cells was 5×10⁸/kg (2.71-11.3×10⁸/kg). Engraftment was defined as absolute neutrophil count >0.5×10⁹/L for 3 successive days and platelet count >20×10⁹/L independent of transfusions. Engraftment was monitored by following complete blood counts, chimerism studies and BM biopsies. In total, 4 patients (2 of 19 patients who underwent reduced intensity conditioning regimen and 2 of 99 patients who underwent myeloablative conditioning regimen) re-infused “back-up” cells at once when the engraft failure was diagnosed. The media interval between allo-HSCT and re-infusion of “Back-up” cells were 39.5 day (range from 24 days to 50 days). The median MNC counts of re-infused cells were 4.49×10⁸/Kg (range from 4.10 to 5.15). 3 of the 4 patients achieved successful hematological reconstitution within 13 days, and the fourth patient was still pancytopenia during 23 days after the re-infusion of “back-up” cells with BM examination revealing severe BM hypoplasia. However, second HSCT from a haploidentical donor following a fludarabine (Flu)- and anti-thymocyte globulin (ATG)-based conditioning regimen resulted in hematological reconstitution. After re-infusion of “Back-up” cells, 2 patients with CML and 1 patient with Ph+ ALL received continuing imatinib treatment and the fourth patient who underwent second haploidentical donor HSCT was watchful waited. One patient who diagnosed with CML was still alive for 4.5 years after the re-infusion of “back-up” cells, and recurrent detection of the expression of BCR/ABL fusion gene showed complete cytogenetic remission. Another CML patient died of progression of disease and intracranial hemorrhages in 7 months after the re-infusion of “back-up” cells The patient who diagnosed with ALL (Ph+) was still alive for 2.3 years after the re-infusion of “back-up” cells, and recurrent bone marrow aspiration examinations showed complete remission. The patient diagnosed with AML and underwent second haploidentical transplantation was alive in CR for 1.8 years. Our experience suggests that re-infusion of cryopreserved “back-up” cells could provide a safe and effective therapeutic strategy for engraftment failure after unrelated allo-HSCT in adult patients.