Single-center clinical research of matched sibiling donor and haploidentical hematopoietic stem cell transplantation for treatment of malignant hematopathy

Objective To evaluate the safety and efficacy of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in the treatment of malignant hematopathy, through comparison with matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT). Methods From January 2011 to May 2015, a total of 68 patients who had accepted related donor hematopoietic stem cell transplantation (HSCT) in Department of Hematology, First Affiliated Hospital of Chongqing Medical University were enrolled into this retrospective study as study subjects. According to different types of related donor HSCT, 68 cases of patients were divided into MSD-HSCT group (n=33) and haplo-HSCT group (n=35). All the cases were conformed to the diagnostic criteria of Standard of Diagnosis and Curative Effect of Hematology (3rd edition). The inclusion criteria of this study: patients' diagnosis were conformed to the diagnostic criteria of malignant hematopathy and clinical data were complete. Exclusion criteria: clinical data were not complete. Clinical data of donors and patients of the two groups were retrospectively analyzed. Implantations of hematopoietic stem cells in two groups after HSCT were tested. HSCT schemes, the number of input hematopoietic stem cells and outcome of engraftment, transplant related complications, overall survival (OS) rate, disease free survival (DFS) rate, incidence of relapse and mortality were compared and analyzed statistically. The study protocol was approved by the Ethical Review Board of Investigation in Human at First Affiliated Hospital of Chongqing Medical University. There were no statistically significant differences of patients' clinical data, such as gender ratio, preprocessing solution type, type of stem cell transplantation and donors' age between two groups (P>0.05). Results ①There were no statistical differences of patients' disease, disease status, blood type between donors and recipients between the two groups (χ2=2.313, 2.809, 3.420; P=0.678, 0.094, 0.331). But the patients in MSD-HSCT group were older than haplo-HSCT group with statistical significance (t=2.534, P=0.010). ②There were no statistical differences of the input of mononuclear cells (MNC)[(15.0±3.8)×108/kg vs (16.3±4.2)×108/kg)]and the CD34+ cells[(5.8±3.1)×106/kg vs (6.8±2.7)×106/kg]between the two groups (t=1.277, 1.062; P=0.206, 0.294). ③In MSD-HSCT group, average time of neutrophils count over 0.5×109/L[(12.7±2.9) d]was significantly earlier than that of haplo-HSCT group[(16.1±4.8) d](t=3.510, P=0.001). Average time of platelets count over 20×109/L[(12.7±4.9]d]was also significantly earlier than that of haplo-HSCT group[(16.1±7.9) d](t=2.094, P=0.016). All of the 68 patients obtained hematopoietic reconstruction and achieved chimeric state. ④There were no statistical differences of cumulative incidence of acute graft versus host disease (aGVHD) (18.2% vs 22.9%), cumulative incidence of chronic graft versus host disease (cGVHD) (39.3% vs 26.9%), incidence of engraftment syndrome (ES) (0 vs 2.9%), hemorrhagic cystitis (HC) (24.2% vs 45.7%), thrombotic microangiopathy (TMA) (3.0% vs 2.9%), hepatic veno-occlusive disease (VOD) (3.0% vs 2.9%), capillary leak syndrome (CLS) (0 vs 2.9%), herpes (24.2% vs 14.3%), bacterial infection (33.3% vs 20.0%), fungal infection (12.1% vs 20.0%), cytomegalovirus (CMV) infection (9.1% vs 5.7%), secondary tumors (3.0% vs 0), reversible posterior leukoencephalopathy syndrome (RPLS) (0 vs 2.9%) between the two groups (χ2=0.227, 1.551, 0.957, 3.429, 0.002, 0.002, 0.957, 1.089, 1.551, 0.778, 0.284, 1.076, 0.957; P=0.634, 0.336, 0.328, 0.064, 0.966, 0.966, 0.328, 0.297, 0.213, 0.378, 0.594, 0.299, 0.328). ⑤Up to September 1st, 2015, there were 21 patients survived in MSD-HSCT group, and the mortality was 36.4%, relapse rate was 18.2%. Mean survival time was (34.7±4.2) months, and OS and DFS rate of 3 years were 60.6%, 56.0%, respectively. Twenty-three patients survived in haplo-HSCT group, and the mortality was 34.3%, relapse rate was 5.7%. Mean survival time was (27.3±3.2) months, and OS and DFS rate of 3 years were 61.9%, 58.5% respectively. There were no statistical differences between relapse rate and mortality between two groups (χ2=2.543, 0.032; P=0.111, 0.858). There was also no statistical difference of mean survival time between two groups (t=1.537, P=0.129). There were no statistical differences between OS and DFS rate of 3 years (χ2=0.137, 0.032; P=0.706, 0.694). Conclusions The hematopoietic reconstruction time of neutrophils and platelets in malignant hematopathy patients who received MSD-HSCT treatment were earlier than those malignant hematopathy patients who received haplo-HSCT treatment, but they got a similar rate of OS, DFS, relapse, mortality and graft versus host disease (GVHD). Safety and efficacy of haplo-HSCT in treatment of malignant hematopathy is similar with MSD-HSCT. Key words: Hematopoietic stem cell transplantation; Hematologic disease; Comparative effectiveness research