Higher CD3+ and CD34+ cell doses in the graft increase the incidence of acute GVHD in children receiving BMT for thalassemia

Gaziev, Javid; Isgrò, Antonella; Marziali, Marco; Daniele, Nicola Di; Gallucci, Cristiano; Sodani, Pietro; Simone, Maria Domenica; Adorno, Gaspare; Paciaroni, Katia; Andreani, Marco; Lanti, Alessandro; Proposto, Gianpaolo Del; Testi, Manuela; Angelis, Gioia De; Roveda, Andrea; Alfieri, Cecilia; Saltarelli, Francesca; Lucarelli, G

doi:10.1038/bmt.2011.3

Cited by 33 publications

(31 citation statements)

References 40 publications

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“…Recent data from Italy reported acute GVHD (Grade 2 --4) rates of 35% with the TRM at 3 years to be significantly higher in patients with acute GVHD (23%) compared with patients with grade 0 --1 acute GVHD (5%, P ¼ 0.013). 31 No death was attributed or related to acute or chronic GVHD in our cohort. It is therefore reasonable to assume that the inclusion of ATG in our regimens contributed substantially to the favorable outcome in our patients by minimizing graft rejection on the one hand and by reducing GVHD on the other.…”

Section: Discussionmentioning

confidence: 99%

HLA-matched sibling stem cell transplantation in children with β-thalassemia with anti-thymocyte globulin as part of the preparative regimen: the Greek experience

Goussetis

Peristeri

Kitra

et al. 2011

Bone Marrow Transplant

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BU combined with CY, the preferred preparatory regimen for thalassemic patients, is associated with a substantial incidence of graft rejection especially in patients with advanced disease stage. This study retrospectively analyzes the outcome of 75 consecutive pediatric patients with b-thalassemia who underwent HLA-matched sibling transplantation after anti-thymocyte globulin (ATG)-containing myeloablative conditioning regimens. With a median follow-up of 9 years (range 1--15 years), the overall survival (OS) and thalassemia free survival (TFS) rates were 96% and 92%, respectively. Both the estimated TRM and the cumulative incidence of rejection/failure were 4%. The cumulative incidences of acute GVHD grade II --III and grade III were 20% and 5.3%, respectively. No patient developed acute GVHD grade IV. Only two patients developed extensive chronic GVHD. The estimated OS and TFS for patients with Class 1 and 2 disease according to Pesaro criteria were 96.3% and 94.4%, whereas for patients with Class 3 disease they were 94.1% and 88.2%, respectively. In our series, the use of myeloablative conditioning regimens, which include ATG for the transplantation of thalassemic children from matched sibling donors, resulted in excellent outcomes with very low incidences of TRM and rejection. INTRODUCTIONDespite considerable progress in the management of thalassemia major over the last three decades resulting in significant improvement in survival, hematopoietic SCT remains the only curative approach for children with b-thalassemia major to date.

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Section: Discussionmentioning

confidence: 99%

HLA-matched sibling stem cell transplantation in children with β-thalassemia with anti-thymocyte globulin as part of the preparative regimen: the Greek experience

Goussetis

Peristeri

Kitra

et al. 2011

Bone Marrow Transplant

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“…11 Comparison of days to neutrophil and platelet engraftment according to cell dose was carried out according to the Mann-Whitney test. Incidence of acute and chronic GVHD, relapse rate and TRM was calculated with the cumulative incidence function.…”

Section: Discussionmentioning

confidence: 99%

Impact of CD34+ cell dose in children who receive unrelated PBSCT with in vivo T-cell depletion for hematologic malignancies

et al. 2014

Bone Marrow Transplant

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PBSCs are increasingly being chosen as the mode of donation among unrelated donors. Pediatric patients, in particular, may receive very high CD34 + and CD3 + doses during unrelated PBSCT. In this work, we analyzed survival and GVHD outcomes in a cohort of 81 children who received unrelated PBSCT with uniform antithymocyte globulin (ATG)-based in vivo T-cell depletion for treatment of hematologic malignancy, with emphasis on the impact of cell dose on transplant outcomes. EFS was 61.5 ± 5.6%, with higher CD34 + dose (410.0 × 10 6 /kg) and lower patient risk status predicting improved survival in multivariate study. Cumulative incidence of relapse was 30.2 ± 5.2%; a low CD34 + dose was the only significant factor for relapse. Neither CD34 + nor CD3 + dose was a significant determinant of acute or chronic GVHD. Importance of CD34 + dose was reaffirmed in a subcohort of younger patients who received greater median cell doses than the overall cohort. In summary, for children who received unrelated PBSCT with ATG-based T-cell depletion for treatment of hematologic malignancy, the CD34 + dose was the most important factor for relapse and EFS, and neither the CD34 + nor the CD3 + dose influenced incidence of acute or chronic GVHD. INTRODUCTIONIn many countries, G-CSF-mobilized PBSCs have become an important cell source in unrelated hematopoietic cell transplantation (UHCT). The relative ease of PBSC collection has resulted in unrelated donors favoring PBSC rather than BM as their mode of donation. Consistent with this predilection for PBSC among unrelated donors, several studies have reported on unrelated PBSCT, mainly in the context of comparing important transplantrelated outcomes to BMT. 1-6 Studies deriving from a mostly adult HCT population, including a recent randomized trial, conclude that unrelated PBSCT results in similar survival when compared with unrelated BMT, but with a greater incidence of chronic GVHD. 1,2 However, several pediatric studies report that with antibody-based T-cell depletion, such as the use of antithymocyte globulin (ATG) or alemtuzumab (Campath), unrelated PBSCT may result in outcomes that are similar to BMT without an increased risk of GVHD, underscoring the notion that PBSC donation may be as valid an option as BM donation for children in the unrelated transplant setting. [3][4][5][6] Despite the significant number of reports indicating comparable outcomes for unrelated PBSCT and BMT among pediatric patients, the literature on PBSCT in children outside the framework of comparisons with BMT is limited. For example, risk factors for both acute and chronic GVHD after PBSCT are not clear. A factor that may have a major impact on pediatric transplant outcomes is the infused cell dose, especially since collection of PBSC results in cell numbers that are far greater than those found in BM, and children, particularly infants, may receive very high cell doses per patient weight. Previous studies on unrelated HCT showed that

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“…35,36 Acute GVHD was described in 11% to 38% and chronic GVHD in 6% to 50% of MFD transplants depending on stem cell source (peripheral blood transplants had a higher GVHD risk than cord blood transplants), with a 15-year OS of 87% and DFS of 70% in MFD HSCT. 33,[37][38][39][40][41][42][43][44][45] With increasingly successful outcomes demonstrated, especially in patients with risk class I and II disease and lowered toxicity following modification in transplant methods, this curative treatment modality should be discussed with all patients with HLA-matched family members following establishment of diagnosis and transfusion dependency, usually by about 2 or 3 years of age.…”

Section: Thalassemia (Case 2)mentioning

confidence: 99%

Evidence-based focused review of the status of hematopoietic stem cell transplantation as treatment of sickle cell disease and thalassemia

King

Shenoy

2014

Blood

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Higher CD3+ and CD34+ cell doses in the graft increase the incidence of acute GVHD in children receiving BMT for thalassemia

Cited by 33 publications

References 40 publications

HLA-matched sibling stem cell transplantation in children with β-thalassemia with anti-thymocyte globulin as part of the preparative regimen: the Greek experience

HLA-matched sibling stem cell transplantation in children with β-thalassemia with anti-thymocyte globulin as part of the preparative regimen: the Greek experience

Impact of CD34+ cell dose in children who receive unrelated PBSCT with in vivo T-cell depletion for hematologic malignancies

Evidence-based focused review of the status of hematopoietic stem cell transplantation as treatment of sickle cell disease and thalassemia

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