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1.
Bull Cancer ; 2024 Mar 13.
Article in French | MEDLINE | ID: mdl-38485627

ABSTRACT

Changing practices and the limited use of cord blood units as a source of cells for allogeneic hematopoietic stem cell transplants (HSC) led us to reconsider the recommendations established in 2011 and 2012, and to propose an update incorporating recent bibliographic data. If HLA compatibility was until now established at low resolution for HLA-A and B loci, and at high resolution for HLA-DRB1, the recent papers are converging towards an increase in the level of resolution, making way for a compatibility now defined in high resolution for all the considered loci, and the inclusion of the HLA-C locus, in order to establish a level of HLA compatibility on 8 alleles (HLA-A, B, C and DRB1). The CD34+ dose is a determining factor in hematopoietic reconstitution but it is not correlated with the total nucleated cells content. This is why we recommend taking these two data into account when choosing a cord blood unit. The recommendations established by our group are presented as a flow chart taking into account the characteristics of the underlying pathology (malignant or non-malignant), the cell dose and the HLA compatibility criteria, as well as criteria linked to the banks in which units are stored.

2.
Acta Oncol ; 60(4): 466-474, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33112687

ABSTRACT

BACKGROUND: The impact of acute graft versus host disease (GVHD) on survivals for patients receiving a haploidentical allogeneic stem-cell transplant (Allo-SCT) with peripheral blood stem-cells (PBSC) complemented by post-transplant cyclophosphamide (PTCY) is ill-known. MATERIAL AND METHODS: This retrospective study included 131 patients who received a PBSC haplograft in order to precise the impact of acute GVHD on outcomes. There were 78 males and 53 females and the median age for the whole cohort was 59 years (range: 20-71). Thirty-five patients were allografted for a lymphoid disease and 96 for a myeloid malignancy, including 67 patients with acute myeloid leukemia (AML). RESULTS: The cumulative incidence (CI) of day 100 grade 2-4 and 3-4 acute GVHD was 43.4 + 4.6% and 16.7 + 3.4%, respectively. The 2-year CI of moderate/severe chronic GVHD was 10.1 + 2.8%. The only factor affecting the occurrence of GVHD was GVHD prophylaxis. Indeed, CI of day 100 grade 2-4 (but not grade 3-4) acute GVHD was significantly reduced when adding anti-thymoglobulin (ATG) to PTCY. However, in multivariate analysis, grade 2 acute GVHD was significantly associated with better disease-free (HR: 0.36; 95%CI: 0.19-0.69, p = .002) and overall (HR: 0.35; 95%CI: 0.1-0.70, p = .003) survivals. The same results were observed when considering only AML patients. CONCLUSION: Acute grade 2 GVHD is a factor of good prognosis after PBSC haplotransplant with PTCY. Further and larger studies are needed to clarify the complex question of GVHD prophylaxis in the setting of haplo-transplant, especially that of combining ATG and PTCY.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Peripheral Blood Stem Cells , Adult , Aged , Cyclophosphamide , Female , Graft vs Host Disease/epidemiology , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Transplantation Conditioning , Young Adult
3.
Sci Rep ; 10(1): 15399, 2020 09 21.
Article in English | MEDLINE | ID: mdl-32958816

ABSTRACT

Graft-versus host disease (GVHD) remains one of the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (ASCT). Prophylactic T cell depletion via antithymocyte globulin (ATG) during ASCT conditioning is one of the standards of care for GVHD prophylaxis, although the optimal dosing strategy is still unclear. Recent studies have reported that absolute lymphocyte count at the time of ATG administration could predict survivals in ASCT from unrelated donors. Here this issue was examined in 116 patients receiving peripheral blood stem cells (PBSC) ASCT with purine analog/busulfan-based conditioning regimens between 2009 and 2019 in our department. The impact of lymphopenia at the time of ATG administration was evaluated in terms of overall survival, disease-free survival and GVHD-free/relapse-free survival. After a median follow-up of 4 years, no adverse effect of a profound lymphopenia was observed on patients' outcome. Notably, a reduced dose of ATG in patients with profound lymphopenia did not translate into better survivals. This study indicates that ATG can be administered whatever the recipient's lymphocyte counts in patients receiving a PBSC purine analog/busulfan-based conditioning regimen ASCT.


Subject(s)
Antilymphocyte Serum/therapeutic use , Lymphopenia/drug therapy , Peripheral Blood Stem Cell Transplantation/methods , Adult , Aged , Allografts , Antilymphocyte Serum/administration & dosage , Antilymphocyte Serum/metabolism , Busulfan/administration & dosage , Disease-Free Survival , Female , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/mortality , Humans , Lymphocyte Depletion , Lymphopenia/etiology , Male , Middle Aged , Peripheral Blood Stem Cells/drug effects , Purine Nucleosides/administration & dosage , Retrospective Studies , Transplantation Conditioning , Transplantation, Homologous
4.
Ann Hematol ; 99(6): 1341-1350, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32342134

ABSTRACT

The influence of peripheral blood stem cell (PBSC) graft cell contents after transplant with post-transplant cyclophosphamide (PTCY) remains unclear. Here, we retrospectively report on a cohort of 77 adults who received a Baltimore-based reduced-intensity conditioning regimen either with fludarabine (n = 40) or clofarabine (n = 37) and PTCY. With a median follow-up of 29.2 months, [2-]year overall (OS), disease-free (DFS), and GVHD/relapse-free survival (GRFS) rates were 62.8%, 51%, and 36.7%, respectively. The incidence of grades [2-]4 acute GVHD was significantly higher in patients transplanted with a haplodonor (n = 56), at 57.1% vs 19% (p = 0.006). PBSC graft cell contents (CD45+, CD34+, and CD3+ cells) had no impact on any outcome. Considering immune reconstitution until 1 year, only monocytes were above the normal range (as early as day + 30) during the first year post-transplant. In multivariate analysis, an older donor (> 45 years) and a high/very high disease risk index were independently associated with lower OS. A higher monocyte count (> median) at day + 90 was also associated with better OS, DFS, and GRFS. Donor/recipient CMV status matching was independently associated with GRFS. In conclusion, our data support the fact that there is no need to manipulate the graft before infusion in the particular context of PBSC/PTCY Baltimore-based allotransplant.


Subject(s)
Antigens, CD34/blood , CD3 Complex/blood , Cyclophosphamide/administration & dosage , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Adult , Aged , Cohort Studies , Female , Follow-Up Studies , Graft Survival/physiology , Hematopoietic Stem Cell Transplantation/trends , Humans , Immunosuppressive Agents/administration & dosage , Male , Middle Aged , Retrospective Studies , Transplantation Conditioning/trends , Treatment Outcome , Young Adult
6.
Biol Blood Marrow Transplant ; 22(8): 1473-1479, 2016 08.
Article in English | MEDLINE | ID: mdl-27118570

ABSTRACT

This single-center retrospective study aimed to report the impact of early hematopoietic and immune recoveries after a standard total body irradiation, cyclophosphamide, and fludarabine (TCF) reduced-intensity conditioning (RIC) regimen for double umbilical cord blood (dUCB) allogeneic stem cell transplantation (allo-SCT) in adults. We analyzed 47 consecutive patients older than 17 years who engrafted after a dUCB TCF allo-SCT performed between January 2006 and April 2013 in our department. Median times for neutrophil and platelet recoveries were 17 (range, 6 to 59) and 37 days (range, 0 to 164), respectively. The 3-year overall (OS) and disease-free survivals, relapse incidence, and nonrelapse mortality were 65.7%, 57.2%, 27.1%, and 19%, respectively. In multivariate analysis, higher day +30 monocyte (≥615/mm(3); hazard ratio [HR], .04; 95% confidence interval [CI], .004 to .36; P < .01) and day +42 lymphocyte (≥395/mm(3); HR, .16; 95% CI, .03 to .78; P = .02) counts were independently associated with better OS. These results suggest that early higher hematopoietic and immune recovery is predictive of survival after dUCB TCF RIC allo-SCT in adults. Factors other than granulocyte colony-stimulating factor, which was used in all cases, favoring expansion of monocytes or lymphocytes, should be tested in the future as part of the UCB transplantation procedure.


Subject(s)
Cord Blood Stem Cell Transplantation/methods , Lymphocytes/cytology , Monocytes/cytology , Transplantation Conditioning/methods , Adolescent , Adult , Aged , Cord Blood Stem Cell Transplantation/mortality , Cyclophosphamide/administration & dosage , Female , Graft Survival , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Leukocyte Count , Lymphocyte Count , Male , Middle Aged , Transplantation Conditioning/mortality , Transplantation, Homologous , Vidarabine/administration & dosage , Vidarabine/analogs & derivatives , Whole-Body Irradiation , Young Adult
7.
Blood ; 127(14): 1828-35, 2016 Apr 07.
Article in English | MEDLINE | ID: mdl-26903546

ABSTRACT

We studied the impact of a set of immune cells contained within granulocyte colony-stimulating factor-mobilized peripheral blood stem cell grafts (naïve and memory T-cell subsets, B cells, regulatory T cells, invariant natural killer T cells [iNKTs], NK cells, and dendritic cell subsets) in patients (n = 80) undergoing allogeneic stem cell transplantation (SCT), using the composite end point of graft-versus-host disease (GVHD)-free and progression-free survival (GPFS) as the primary end point. We observed that GPFS incidences in patients receiving iNKT doses above and below the median were 49% vs 22%, respectively (P= .007). In multivariate analysis, the iNKT dose was the only parameter with a significant impact on GPFS (hazard ratio = 0.48; 95% confidence interval, 0.27-0.85;P= .01). The incidences of severe grade III to IV acute GVHD and National Institutes of Health grade 2 to 3 chronic GVHD (12% and 16%, respectively) were low and associated with the use of antithymocyte globulin in 91% of patients. No difference in GVHD incidence was reported according to the iNKT dose. In conclusion, a higher dose of iNKTs within the graft is associated with an improved GPFS. These data may pave the way for prospective and active interventions aiming to manipulate the graft content to improve allo-SCT outcome.


Subject(s)
Antilymphocyte Serum/administration & dosage , Graft vs Host Disease , Natural Killer T-Cells/immunology , Natural Killer T-Cells/pathology , Stem Cell Transplantation , Adolescent , Adult , Aged , Allografts , Child , Chronic Disease , Disease-Free Survival , Female , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Graft vs Host Disease/pathology , Graft vs Host Disease/prevention & control , Humans , Male , Middle Aged , Retrospective Studies , Survival Rate
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