Moazzam Shahzad1, Raheel S Siddiqui2, Iqra Anwar3, Sibgha Gull Chaudhary3, Tayyaba Ali3, Masooma Naseem4, Tehniat F Ahmed3, Zahoor Ahmed3, Sharad Khurana5, Nausheen Ahmed3, Ramesh Balusu3, Anurag K Singh3, Peiman Hematti6, Natalie S Callander6, Sunil H Abhyankar3, Joseph P McGuirk3, Muhammad Umair Mushtaq7. 1. Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS; Department of Medicine, St Mary's Medical Center, Huntington, WV. 2. Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS; Department of Medicine, Icahn School of Medicine at Mount Sinai/Queens, Jamaica, NY. 3. Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS. 4. Department of Medicine, Icahn School of Medicine at Mount Sinai/Queens, Jamaica, NY. 5. Division of Hematology & Oncology, University of Arizona College of Medicine, Tucson, AZ. 6. Division of Hematology & Oncology, University of Wisconsin School of Medicine & Public Health, Madison, WI. 7. Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS. Electronic address: mmushtaq@kumc.edu.
Abstract
BACKGROUND: Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) characterized by multilineage cytopenia in the absence of mixed donor chimerism (<95% donor), relapse, or severe graft-vs-host disease (GVHD). We present a systemic review and meta-analysis aimed to assess the outcomes with CD34-selected stem cell boost (SCB) for PGF in adult allo-HSCT patients. METHODS: We screened a total of 1753 records identified from 4 databases (PubMed, Embase, Cochrane, and Clinical trials.gov) following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using search terms for "hematological malignancies", "hematopoietic stem cell transplantation", "CD34 antigen(s)", "graft failure" and "poor graft function" from the date of inception to January 2021. After excluding review, duplicate, and non-relevant articles, we included 7 studies reporting outcomes following administration of CD34-selected SCB for PGF after allo-HSCT, including hematologic complete response (CR) and overall response rate (ORR), GVHD, and overall survival (OS). Quality evaluation was done using the NIH quality assessment tool. Pooled analysis was done using the 'meta' package (Schwarzer et al, R programming language) and proportions with 95% confidence intervals (CI) were computed. The inter-study variance was calculated using Der Simonian-Laird Estimator. RESULTS: We identified 209 patients who received CD34-selected SCB for PGF after allo-HSCT. The median age was 49 (18-69) years and 61% were men. Primary graft sources included peripheral blood stem cells (72%) and bone marrow graft (28%). Donor types were matched sibling (37%), matched unrelated (36%), mismatched unrelated (22%), and haploidentical donors (5%). Median time since transplant to SCB was 138 (113-450) days. Median SCB dose was 3.45 (3.1-4.9) million CD34 cells/kg. CR and ORR were 72% (95%CI 0.63-0.79, I2=26%) and 80% (95% CI 0.74-0.85, I2=0%) respectively. After median follow up of 42 (30-77) months, actuarial survival rate (ASR) was 54% (95%CI 0.47-0.61, I2= 0%). OS was reported from 80% at 1 year to 40% at 9 years. Acute and chronic GVHD incidence after SCB was 17% (95% CI 0.13-0.23, I2=0%) and 18% (95% CI 0.08-0.34, I2=76%) respectively. Non-relapse mortality was reported in 42 patients with pooled rate of 27% (95% CI 0.17-0.40, I2=59%) while death due to relapse was reported in 25 patients with a pooled rate of 17% (95% CI 0.11-0.23, I2=0%). CONCLUSION: CD34-selected SCB improves outcomes after PGF post allo-HSCT with an acceptable toxicity profile. Current literature lacks high-quality randomized evidence and there remains an unmet need for prospective studies to address optimal dosing and manipulation of SCB.
BACKGROUND: Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) characterized by multilineage cytopenia in the absence of mixed donor chimerism (<95% donor), relapse, or severe graft-vs-host disease (GVHD). We present a systemic review and meta-analysis aimed to assess the outcomes with CD34-selected stem cell boost (SCB) for PGF in adult allo-HSCT patients. METHODS: We screened a total of 1753 records identified from 4 databases (PubMed, Embase, Cochrane, and Clinical trials.gov) following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using search terms for "hematological malignancies", "hematopoietic stem cell transplantation", "CD34 antigen(s)", "graft failure" and "poor graft function" from the date of inception to January 2021. After excluding review, duplicate, and non-relevant articles, we included 7 studies reporting outcomes following administration of CD34-selected SCB for PGF after allo-HSCT, including hematologic complete response (CR) and overall response rate (ORR), GVHD, and overall survival (OS). Quality evaluation was done using the NIH quality assessment tool. Pooled analysis was done using the 'meta' package (Schwarzer et al, R programming language) and proportions with 95% confidence intervals (CI) were computed. The inter-study variance was calculated using Der Simonian-Laird Estimator. RESULTS: We identified 209 patients who received CD34-selected SCB for PGF after allo-HSCT. The median age was 49 (18-69) years and 61% were men. Primary graft sources included peripheral blood stem cells (72%) and bone marrow graft (28%). Donor types were matched sibling (37%), matched unrelated (36%), mismatched unrelated (22%), and haploidentical donors (5%). Median time since transplant to SCB was 138 (113-450) days. Median SCB dose was 3.45 (3.1-4.9) million CD34 cells/kg. CR and ORR were 72% (95%CI 0.63-0.79, I2=26%) and 80% (95% CI 0.74-0.85, I2=0%) respectively. After median follow up of 42 (30-77) months, actuarial survival rate (ASR) was 54% (95%CI 0.47-0.61, I2= 0%). OS was reported from 80% at 1 year to 40% at 9 years. Acute and chronic GVHD incidence after SCB was 17% (95% CI 0.13-0.23, I2=0%) and 18% (95% CI 0.08-0.34, I2=76%) respectively. Non-relapse mortality was reported in 42 patients with pooled rate of 27% (95% CI 0.17-0.40, I2=59%) while death due to relapse was reported in 25 patients with a pooled rate of 17% (95% CI 0.11-0.23, I2=0%). CONCLUSION:CD34-selected SCB improves outcomes after PGF post allo-HSCT with an acceptable toxicity profile. Current literature lacks high-quality randomized evidence and there remains an unmet need for prospective studies to address optimal dosing and manipulation of SCB.