CD34+ Selected Cells "Boost" for Poor Graft Function Post Allogeneic Stem Cell Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2300-2300
Author(s):  
Razan Mohty ◽  
Annalisa Ruggeri ◽  
Giorgia Battipaglia ◽  
Florent Malard ◽  
Eolia Brissot ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Graft Function ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Post Infusion ◽  
Poor Graft Function ◽  
Clinically Significant

Abstract Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used in the treatment of a variety of hematologic diseases. However, allo-HSCT can be associated with many complications, including poor graft function early after transplant requiring long-lasting supportive care. In the literature, the incidence of poor graft function post allo-HSCT has been reported to range from 4 to 27%. Here, we retrospectively studied 10 patients (male/female: 4/6, median age: 45 years, range 19 to 67) who received a boost of CD34+ selected cells for poor graft function after allo-HSCT (of whom 4 cases of haplo-identical allo-HSCT with post-Cy prophylaxis), between January 2014 and January 2016. Patients' disease and transplant characteristics are summarized in the below table. Patients were selected for the CD34+ cells "boost" therapy after eliminating other causes that could explain a poor graft function (eg. drug toxicity, infections, disease relapse, etc.) The same original allo-HSCT donor was used to collect the CD34+ cells after mobilization with G-CSF and positive selection. The patients did not receive any prior conditioning therapy prior to CD34+ cells boost infusion. At time of the boost, all patients were in full donor chimerism. The number of infused CD34+ cells differed from one patient to another ranging from 2.91 to 7.99 x106 cells/kg recipient body weight. The median day of infusion post- allo-HSCT was 120 (range, 76-352). Among these 10 patients, 7 patients had full counts recovery at a median of 15 days (range, 7-30) post-infusion, while 3 patients had an incomplete response with persistent anemia and/or thrombocytopenia. None of the patients experienced clinically significant GVHD symptoms after the boost. At last follow-up, 7 patients were alive whereas 3 patients died of severe infections after 1, 6 and 13 months post-boost. Based on these results, we concluded that boost therapy can be used in the treatment of poor graft function post-allogeneic HSCT, including in those patients who received a haplo-transplant. Disclosures No relevant conflicts of interest to declare.

CXCR4 allelic Variations Influence Hematological Recovery Following Autologous Stem Cell Transplantation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4098-4098 ◽  
Author(s):  
María L. Lozano ◽  
Elkin A. Niño ◽  
Juan Jose Cerezo ◽  
Cristina Castilla-Llorente ◽  
Ana I. Anton ◽  
...  
Keyword(s):  
Stem Cell ◽  
Alternative Splicing ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Predictive Factor ◽  
Conflicts Of Interest ◽  
Hematopoietic Stem ◽  
Platelet Recovery ◽  
Cd34 Cells

Abstract Abstract 4098 Introduction. The ability to achieve rapid and sustained myeloid and platelet engraftment is a major determinant for outcome in patients undergoing autologous stem cell transplantation (ASCT). The CXCR4 chemokine receptor, present in hematopoietic progenitors (HPs), and its ligand, stromal cell-derived factor 1 (SDF-1) play a pivotal role in retaining HPs within the bone marrow microenvironment in the adult. Recently, the intronic single nucleotide polymorphism (SNP) rs2680880 in CXCR4 located close to a region implicated in alternative splicing that generates 2 variants, has been associated with peripheral blood progenitor cell (PBPC) mobilization success among healthy donors (Haematologica 2011; 96: 102–109). Aim. To evaluate the influence of rs2680880 polymorphism in CXCR4 on engraftment of PBPC in patients undergoing ASCT. Patients and Methods. A total of 144 ASCT patients were included (60 lymphoma, 60 multiple myeloma, 24 acute leukemia). The median dose of PBPC infused was 2.6 x106 CD34+ cells/kg. Myeloid and platelet recovery after transplant were evaluated by daily CBC. The rs2680880 polymorphism was genotyped by allelic discrimination polymerase chain reaction (PCR) assays using TaqMan®Genotyping Assays (Applied Biosystems). Results. Allelic frequencies were 0.64 for A allele and 0.36 for T allele, being 13% of patient TT homozygous. Notably, when analyzing the subgroup of 136 patients that had been infused with a yield of CD34+ cells below the 95th percentile (<6.8×106/kg CD34+ cells) the presence of the T variant in homocygosis was related with a significant delayed myeloid and platelet engraftment compared to AA+AT genotypes. Thus, TT homozygotes exhibited slower leukocyte recovery, (neutrophils >0.5×109/L [15 vs. 12 days, p=0.022], neutrophils >1×109/L [16 vs. 13 days, p=0.023). Platelet engraftment was similarly delayed (>20 × 109/L and >50 × 109/L [18 vs. 13 days, p=0.038; 23 vs. 17 days, p=0.016, respectively]). The T allele in heterozygosity did not have any influence on these variables. A multivariate analysis considering age, disease, low platelet/leukocyte count before mobilization, rs2680880 polymorphism in CXCR4 and number of CD34+ cells infused, showed that the best predictive factors for delayed platelet recovery were the number of infused CD34+ cells and the presence of the T variant in homozygosis. Remarkably, homozygosis for T allele in CXCR4 was found to be the main and only predictive factor for neutrophil engraftment. Discussion. Some patients exhibit delayed recoveries after ASCT despite a sufficient number of CD34+ cells administered in a clinically stable situation. We find that a homozygous common variant (rs2680880[T]) that could modulate the alternative splicing in CXCR4 to produce shorter transcripts, is a strong predictor of engraftment. A high number of CD34+ infused cells probably disguise or lessen the effect of the TT allelic variant of CXCR4 gene on PBPC homing. Because the migration of hematopoietic stem cells is a complex process that involves the CXCR4/SDF-1 axis, we speculate that this genetic marker could be associated to poorer mobilization responses to plerixafor. This is the first study, to our knowledge, to describe a genetic variable as a potential predictive factor in the hematological recovery after ASCT. Funding. This study was supported in part by a research grants 04515/GERM/06; RECAVA RD06/0014/0039, and FIS 10/02594. Disclosures: No relevant conflicts of interest to declare.

Outcomes with CD34 stem cell boost for poor graft function after allogeneic hematopoietic stem cell transplantation for hematologic malignancies: A systemic review and meta-analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19021-e19021
Author(s):  
Moazzam Shahzad ◽  
Iqra Anwar ◽  
Raheel Sufian Siddiqui ◽  
Tehniat Faraz Ahmed ◽  
Mahrukh Majeed ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Meta Analysis ◽  
Graft Function ◽  
Systemic Review ◽  
Hematopoietic Stem ◽  
Poor Graft Function

e19021 Background: Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HCT) characterized by severe multilineage cytopenia in the absence of mixed donor chimerism, relapse, or severe graft-vs-host disease (GVHD). We present a systemic review and meta-analysis aimed to assess the outcomes with stem cell boost (SCB) for PGF in adult allo-HCT patients. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, 752 articles were screened from 4 databases (PubMed, Embase, Cochrane, and Clinical trials.gov) using MeSH terms and keywords for “hematological malignancies”, “hematopoietic stem cell transplantation”, “CD34 antigen(s)” and “treatment outcome(s)” from the date of inception to Jan 2021. After excluding review, duplicate and non-relevant articles, we included 8 studies (1 prospective, 7 retrospective) reporting hematologic complete/overall response rate (CR/ORR), GVHD and overall survival (OS) after SCB for PGF after Allo-HSCT. 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. Inter-study variance was calculated using Der Simonian-Laird Estimator. Results: We identified 217 patients who received SCB for PGF after allo-HCT. Median age, time since transplant and SCB dose were 48 (37-54) years, 133 (113-450) days and 3.43 (1.7-4.9) million CD34 cells/kg respectively. CR and ORR were 71% (95%CI 0.63-0.77, I216%) and 80% (95%CI 0.74-0.85, I20%) respectively. After median follow up of 41.5 (5-77) months, actuarial survival rate (ASR) was 54% (95%CI 0.48-0.61, I20%). OS was reported from 80% (1y) to 40% (9y) Acute and chronic GVHD incidence after SCB was 17% (95% CI 0.12-0.23, I2=0%) and 17% (95% CI 0.08-0.32, I2=72%, n=197) respectively, and 25% (95% CI 0.14-0.39, I2=63%, n=163) deaths were due to relapse (Table). Conclusions: CD34 SCB improves outcomes after PGF after allo-HSCT with acceptable toxicity profile. However, current literature lacks high-quality randomized evidence and there remains an unmet need for prospective studies to address optimal dosing and manipulation of SCB. Outcomes with SCB for PGF after allo-HCT (n=217).[Table: see text]

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