CD 34 stem cell boost in patients with poor graft function after allogeneic hematopoietic stem cell transplantation: Experience from a tertiary care center

Abstract

Abstract Introduction: Poor hematopoietic reconstitution (PHR), in the form of poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). The CD34+ -selected stem cell boost (SCB) is known to potentially reconstruct hematopoietic stem / progenitor cells in patients with PHR; however, data on safety and efficacy of CD34+ SCB is still evolving. In this study we present our experience on CD34+ SCB in patients with PGF post-HSCT. Method: Patients with PGF, post-HSCT who received a donor CD34+ -selected SCB at National Gaurds Hospital, Riyadh,Saudi Arabia were retrospectively analyzed. Data on hematopoietic response, incidence of acute complication such as graft-versus-host-disease (GVHD), and survival post-CD34+ SCB was collected. Descriptive statistics were used to summarize all data. Categorical variables were summarized using frequencies and percentages, while continuous variables were summarized using median and range. Wilcoxon signed-rank test was used to compare the number of packed red blood cell (pRBC) and platelet transfusions, p-value of < 0.05 was considered statistically significant. Results: In total nine-patients were analyzed involving 56% females (5) and 44% males (4), with a median age of 11 (7 to 44) years. Patients underwent haplo-identical HSCT in 67% (6), full-matched donor in 22% (2) and one-patient (11%) post CAR-T cell infusion following haplo-identical HSCT. Hematologic disorders were the major underlying cause in 78% (7) patients that included leukaemia (n=3,) sickle cell disease (n=3) and thalassemia major (n=1); while two-patients (22%) were with immune deficiencies that included ZAP-70 deficiency (n=1) and CARMIL-2 deficiency (n=1). All patients had received myeloablative conditioning. Refractory PHR diagnosed in our patient cohort was primary PGF with pancytopenia in 45% (4), thrombocytopenia in 33% (3) and bicytopenia (neutropenia and thrombocytopenia) in 22% (2) patients. Prior to CD34+-selected SCB, incidence of Grade II-III, acute graft-versus-host-disease (GVHD) was 33% (3) patients and acute infections were observed in all the nine-patients with CMV re-activation in seven-patients. All patients were treated for PHR with thrombopoietin receptor agonists and supportive care prior to the CD 34+ - selected SCB. The median time to the donor CD34+ SCB was 127 (range:57 to 471) days. The original donor was mobilized using granulocyte colony-stimulating factor(G-CSF) and peripheral blood stem cells were collected from the donor. The CliniMACS prodigy system was used for CD34+ cell sorting and cells were stored in a freezer at 4oC with infusion being completed with 24 hours without cryopreservation. The median number of CD34+ cells infused were 11.15 (range: 5.01 to 19.15) x 106 cells /kg and the median CD3+ cell content was 1.46 (range: 1.00 to 9.89) x 103cells/kg. The final products median CD34+ cell and TNC viability were 98.4% and 97.9%, respectively. None of the patients experienced any notable infusion-related adverse reactions. Conditioning was not used in all the Nine-patients during the CD34+ SCB. The original immunosuppressive therapy and other treatments remained unchanged during or after the SCB. Four-patients never had neutrophil count below 20 x 109/L and the median time to neutrophil engraftment post CD34+ SB was 46 (range: 17 to 34) days in the other four-patients; while one-patient never recovered and had a second transplant due to disease relapse. The median time to platelet engraftment was 39 (range: 17 to 128) days. None of the patients developed aGVHD. The median follow-up of the nine-patients was 189 (range: 38 to 610) all patients have achieved completed hematologic response. Two-patients passed away as one-patient succumbed to leukaemia-disease relapse and another patient had an accidental death due to a car crash. The surviving seven -patients were independent of GCSF and showed a significant decrease in pRBC transfusion (median: 1 per week vs. 0 per week, p-value=0.008) and platelet transfusion (median: 3 per week vs. 0 per week, p-value=0.031). At latest contact all patients are maintaining full donor cell chimerism of > 95%. Conclusion: In our experience CD 34+ SCB emerged as a potentially safe and effective treatment option in patients with PGF after allogeneic HSCT.