Outcomes with CD34-Selected Stem Cell Boost for Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

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-versus-host disease (GVHD). We present a systemic review and meta-analysis aimed at assessing the outcomes with CD34-selected stem cell boost (SCB) for PGF in adult allo-HSCT recipients. We screened a total of 1753 records identified from 4 databases (PubMed, Embase, Cochrane, and ClinicalTrials.gov) following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using the search terms "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 nonrelevant 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 National Institutes of Health quality assessment tool. Pooled analysis was done using the R 'meta' package, and proportions with 95% confidence intervals (CIs) were computed. The inter-study variance was calculated using the Der Simonian-Laird estimator. We identified 209 patients who received CD34-selected SCB for PGF after allo-HSCT. The median age was 49 years (range, 18 to 69 years), and 61% were men. Primary graft sources included peripheral blood stem cells (72%) and bone marrow (28%). Donor types were matched sibling (37%), matched unrelated (36%), mismatched unrelated (22%), and haploidentical donors (5%). The median time from allo-HSCT to SCB was 138 days (range, 113 to 450 days). The median SCB dose was 3.45 × 106 CD34 cells/kg (range, 3.1 to 4.9 × 106 cells/kg). CR and ORR were 72% (95% CI, 63% to 79%; I2 = 26%) and 80% (95% CI, 74% to 85%; I2 = 0%), respectively. After a median follow-up of 42 months (range, 30 to 77 months), the actuarial survival rate was 54% (95% CI, 47% to 61%; I2 = 0%). OS ranged from 80% at 1 year to 40% at 9 years. The incidences of acute and chronic GVHD after SCB were 17% (95% CI, 13% to 23%; I2 = 0%) and 18% (95% CI, 8% to 34%; I2 = 76%), respectively. Nonrelapse mortality was reported in 42 patients, with a pooled rate of 27% (95% CI, 17% to 40; I2 = 59%), and death due to relapse was reported in 25 patients, with a pooled rate of 17% (95% CI, 11% to 23%; I2 = 0%). Our data show that CD34-selected SCB improves outcomes after PGF post allo-HSCT with an acceptable toxicity profile. The literature lacks high-quality randomized evidence, and there remains an unmet need for prospective studies to address the optimal dosing and manipulation of SCB. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

[Effects of CD34(+) selected stem cells for the treatment of poor graft function after allogeneic stem cell transplantation].

Objective: To evaluate the efficacy and safety of purified CD34(+) stem cell boost in the treatment of poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (HSCT) . Methods: 12 patients with poor graft function, reported in our hospital during January 2014 to March 2018, were retrospectively analyzed; The donors of 12 patients were HLA mismatched family members, and all treated with donor purified CD34(+) stem cell after G-CSF mobilization, calculating and statistical analyzing the purity of separation and the recovery rate of CD34(+) stem cells. The related complications and the recovery of blood cells after infusion were observed. Results: The purity of CD34(+) cells in the separation products was 92.0% (44.0%-97.0%) , and the recovery rate was 55.0% (45.0%-96.7%) . The median number of CD34(+) cells was 1.9 (0.9-4.4) ×10(6)/kg with CD3(+) cells as 0.6 (0.3-2.0) ×10(4)/kg. The median durations of white blood cells, platelet and red blood cells recoveries were 18 (14-39) , 29 (16-153) and 60 (9-124) days, respectively. All 12 patients didn't experience serious adverse reactions in the process of infusion, 10 patients achieved hematopoietic recovery, 1 case partial remission, 1 case no recovery, without occurrence of aggravated infection, graft versus host disease and other complications. Conclusion: The infusion of donor purified CD34(+) stem cell was a safe and effective method for PGF after allogeneic HSCT.

Effects of CD34(+) selected stem cells for the treatment of poor graft function after allogeneic stem cell transplantation / 中华血液学杂志

Objective: To evaluate the efficacy and safety of purified CD34(+) stem cell boost in the treatment of poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (HSCT) . Methods: 12 patients with poor graft function, reported in our hospital during January 2014 to March 2018, were retrospectively analyzed; The donors of 12 patients were HLA mismatched family members, and all treated with donor purified CD34(+) stem cell after G-CSF mobilization, calculating and statistical analyzing the purity of separation and the recovery rate of CD34(+) stem cells. The related complications and the recovery of blood cells after infusion were observed. Results: The purity of CD34(+) cells in the separation products was 92.0% (44.0%-97.0%) , and the recovery rate was 55.0% (45.0%-96.7%) . The median number of CD34(+) cells was 1.9 (0.9-4.4) ×10(6)/kg with CD3(+) cells as 0.6 (0.3-2.0) ×10(4)/kg. The median durations of white blood cells, platelet and red blood cells recoveries were 18 (14-39) , 29 (16-153) and 60 (9-124) days, respectively. All 12 patients didn't experience serious adverse reactions in the process of infusion, 10 patients achieved hematopoietic recovery, 1 case partial remission, 1 case no recovery, without occurrence of aggravated infection, graft versus host disease and other complications. Conclusion: The infusion of donor purified CD34(+) stem cell was a safe and effective method for PGF after allogeneic HSCT.

Effects of CD34+ selected stem cells for the treatment of poor graft function after allogeneic stem cell transplantation / 中华血液学杂志

Objective@#To evaluate the efficacy and safety of purified CD34+ stem cell boost in the treatment of poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (HSCT) .@*Methods@#12 patients with poor graft function, reported in our hospital during January 2014 to March 2018, were retrospectively analyzed; The donors of 12 patients were HLA mismatched family members, and all treated with donor purified CD34+ stem cell after G-CSF mobilization, calculating and statistical analyzing the purity of separation and the recovery rate of CD34+ stem cells. The related complications and the recovery of blood cells after infusion were observed.@*Results@#The purity of CD34+ cells in the separation products was 92.0% (44.0%-97.0%) , and the recovery rate was 55.0% (45.0%-96.7%) . The median number of CD34+ cells was 1.9 (0.9-4.4) ×106/kg with CD3+ cells as 0.6 (0.3-2.0) ×104/kg. The median durations of white blood cells, platelet and red blood cells recoveries were 18 (14-39) , 29 (16-153) and 60 (9-124) days, respectively. All 12 patients didn’t experience serious adverse reactions in the process of infusion, 10 patients achieved hematopoietic recovery, 1 case partial remission, 1 case no recovery, without occurrence of aggravated infection, graft versus host disease and other complications.@*Conclusion@#The infusion of donor purified CD34+ stem cell was a safe and effective method for PGF after allogeneic HSCT.

Poor graft function can be durably and safely improved by CD34+-selected stem cell boosts after allogeneic unrelated matched or mismatched hematopoietic cell transplantation.

PURPOSE: Insufficient production of leukocytes, thrombocytes and erythrocytes after allogeneic peripheral blood stem cell transplantation (PBSCT) represents a life-threatening complication. METHODS: In 20 adult patients with poor graft function (PGF defined as transfusion-dependent platelet counts <20,000/µl, or leukocytes <1500/µl, or transfusion-dependent anemia) and variable causes of PGF after allogeneic PBSCT, immunomagnetically selected CD34(+) stem cell boosts (SCB) from matched unrelated (n = 8), mismatched unrelated (n = 11) or haploidentical (n = 1) donors were applied without prior conditioning. RESULTS: Patients received a median of 4.6 × 10(6) CD34(+) cells per kilogram bodyweight (1.9-9.1 × 10(6)) and low T cell numbers (median 0.2 × 10(4), range 0.04-0.6 × 10(4)). All patients showed responses in at least one hematopoietic lineage. Engraftment for platelets, leukocytes and hemoglobin was 88, 88 and 100 % after a median of 14, 13 and 18 days, respectively. With regard to the complete cohort, 90 % (n = 18) showed an increase in platelets (median 76,500/µl, range -7000 to 223,000/µl), 95 % (n = 19) had an increase in leukocytes (median 3110/µl, range 150-13,740/µl) and 90 % (n = 18) improved with regard to hemoglobin (median 1.9 g/dl, range -0.9 to 5.1 g/dl). Due to effective T cell depletion, only one patient developed graft versus host disease (GvHD, grade III) after SCB. Patients were followed for a median of 7.5 months (1-74 months) with 11 patients being alive and disease free with normalized peripheral blood counts at the end of follow-up. CONCLUSIONS: CD34(+)-selected SCB are safe and effective and can durably improve PGF even in patients receiving grafts from unrelated matched or mismatched donors with low incidence of GvHD.

Two Cases of Cytomegalovirus Pneumonia after CD34 Selected Autologous Stem Cell Transplantation

Cytomegalovirus (CMV) pneumonia is an important cause of treatment related mortality after allogeneic stem cell transplantation (SCT) and autologous SCT, particularly in a CD34 selected setting. There is little known about the immune reconstitution pertaining to the CMV after CD34 selected SCT. However, several studies have suggested there is more profound immunodeficiency early in the CD34 selected population compared with the unselected population. We encountered two fatal cases of CMV pneumonia at the CD34 selected SCT for T-cell lymphoblastic lymphoma and high-risk breast cancer that was confirmed through a lung biopsy and bronchoalveolar lavage. In conclusion, autologous CD34 selected CMV seropositive recipients need to be monitored in a similar manner to allogeneic recipients.