Primary Engraftment Failure in Patients with Hematologic Malignancies Undergoing Autologus Hematopoietic Stem Cell Transplantation: Risk Factors Analysis

Background : Autologus hematopoietic stem cell transplantation (auto-HSCT) has now been widely used in treatment ofhematologic malignancies, some solid tumor, and autoimmune diseases and so on. Engraftment failure (EF) is a severe complication after auto-HSCT, and is occurring in 2% to 9.5% of patients. Although this complication is becoming increasingly uncommon with the wide application of mobilized peripheral blood stem cells (PBSCs) instead of bone marrow (BM), it is still associated with considerable morbidity and mortality related to an increasing risk of hemorrhagic complications and infections. In this study, we retrospectively analyzed risk factors of primary EF after auto-HSCT.

Method: For the purpose of this study, EF was defined as an absolute neutrophil count (ANC)≦0.5×10⁹/L and a platelet (PLT) count≦20×10⁹/L for at least 35 consecutive days post-transplantation, with hypoplastic BM and without primary disease relapse. Two hundred and five patients undergoing auto-HSCT from Nanfang Hospital of Southern Medical University, Guangzhou General Hospital of Guangzhou Military Command and Zhongshan City People’s Hospital of Guangdong Province, were included in this study between March 2004 and March 2014. They were divided into two groups according to the presence (EF group) or absence (non-EF group) of primary EF. The clinical and transplantation-related characteristics were collected and compared between groups. Then we would choose some factors to perform a risk analysis for EF.

Results: The median age of 205 patients was 39 years (range 14 to 60 years). Primary diseases included acute myelogenous leukemia (n=120), non-Hodgkin lymphoma (n=49), multiple myeloma (n=36). Eighteen patients (8.78%) developed primary EF after auto-HSCT. There were significant differences regarding infection during the period from transplantation to hematopoietic reconstruction or EF, and the doses of CD34+ cells infused between groups (P values were 0.010 and 0.044). Results of univariate models of binary logistic regression analysis showed that the number of chemotherapy cycles, infection during the period from transplantation to hematopoietic reconstruction or EF and the doses of CD34+ cells infused were related to primary EF after auto-HSCT (P values were 0.017, 0.040 and 0.018). The results of multivariate analysis for the above 3 factors showed that too much chemotherapy cycles pre-transplantation (P=0.032, odds ratio [OR] = 3.140, 95% confidence interval [CI], 1.101 to 8.956) was a risk factor for primary EF after auto-HSCT and the number of CD34+ cells transfused was a protective factor for it (P=0.035, OR= 3.249, 95% CI, 1.088 to 9.704). The 5-year overall survival, disease-free survival and cumulative incidence of tumor relapse post-transplantation were 68.3% (95% CI, 60.6%-76.0%), 63.0% (95% CI, 58.0%-68.0%) and 37.0% (95% CI, 32.0%-42.0%).

Conclusion: The number of chemotherapy cycles is a risk factor for primary EF after auto-HSCT, which may be due to the damaged BM microenvironment by chemotherapy drugs. However, the number of CD34+ cells transfused is a protective factor for it.