Antithymocyte Globulin and Role Of Stem Cell Source On Outcome In Myeloablative Conditioning Of Allogeneic Hematopoietic Stem Cell Transplantation With Identical Sibling and Matched Unrelated Donors - A Retrospective Study Of French Society Of Bone Marrow Graft Transplantation and Cellular Therapy -

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3382-3382
Author(s):  
Aurélie Ravinet ◽  
Aurélie Cabrespine ◽  
Regis Peffault de la Tour ◽  
Mauricette Michallet ◽  
Ibrahim Yakoub-Agha ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Antithymocyte Globulin ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Cell Source

Abstract Objectives Allogeneic hematopoietic stem cell transplantation (AHSCT) is an effective treatment modality for a number of hematological malignancies. Several retrospective studies demonstrate that the addition of antithymocyte globulin (ATG) to standard GvHD prophylaxis in myeloablative conditioned AHSCT resulted in a reduction of the incidence of acute and chronic GvHD. However the impact of rabbit ATG incorporated within a standard myeloablative conditioning regimen (MAC) prior to AHSCT on overall survival (OS) has never been clearly assessed. The purpose of this study is to evaluate retrospectively the long term influence of ATG on OS in a large cohort. Methods All AHSCT with matched sibling donor (MSD) and matched unrelated donor (MUD) performed between 2001-2010 in France and reported to Promise database were retrospectively studied. Patients fulfilling the requirements for this study had received a MAC such as total body irradiation (TBI)-cyclophosphamide or busulfan-cyclophosphamide (Bu-Cy) with or without ATG. Results 1980 AHSCT were reported in 32 transplant centers. One hundred and fifty (8%) patients received ATG (25 with MSD and 125 with MUD), whereas 1830 (92%) did not receive ATG (1441 with MSD and 389 with MUD). Diagnosis were 1452 acute leukemia (73%), 340 myelodysplasia (MDS) and/or myeloproliferative syndrome (MPS) (17%), 157 lymphoma (8%), 9 myeloma and 21 chronic lymphocytic leukemia (CLL) (2%). 1385 patients received a TBI 12 Gy based regimen with cyclophosphamide whereas 595 patients received Bu-Cy. Bone marrow (1468 patients) or peripheral blood stem cells (512 patients) were infused 24-48h after the last cyclophosphamide administration (day 0). Median age at transplantation was 37.5 years in the ATG group and 39.2 years in the non ATG group. Median follow-up was of 79.8 months [19.2-138.8]. Using multivariable analysis, OS was adversely significantly influenced by age of recipient older than 39.1 years, bone marrow stem cell source, MUD, non-complete remission status before HSCT, GvHD grade 2-4, age of donor older than 38.3 years and the use of GvHD prophylaxis other than cyclosporine and methotrexate. ATG was not an independent variable influencing OS. The use of different model of multivariate analyses including propensity score trends to demonstrate that the influence of ATG on OS remain strongly correlated to donor type (MSD vs MUD). According to our results, patient with MSD presented better OS (not reached) than patient with MUD (37 months) (p<0.01). Interestingly, OS rates were lower in the ATG group compared to the non ATG group for patients who received bone marrow (median OS 81 months vs 112 months p=0.033). In this group, in the long term, patients who received ATG trend to have more relapse (median PFS 22 months vs 69 p=0.015). This difference is not observed for patient who received peripheral blood (PB), probably because PB induces more GvHD (49% vs 41%, p=0.001), which is usually correlated with less relapse. In this group, the use of ATG or not has no impact on OS. Conclusion The use of ATG does not influence OS. However, this use is strongly influenced by stem cell source with a negative impact of ATG for the group of patients who received BM. Its usefulness should be discussed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals What Is the Most Appropriate Source for Hematopoietic Stem Cell Transplantation? Peripheral Stem Cell/Bone Marrow/Cord Blood

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Itır Sirinoglu Demiriz ◽  
Emre Tekgunduz ◽  
Fevzi Altuntas
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Cell Source ◽  
Selection Of

The introduction of peripheral stem cell (PSC) and cord blood (CB) as an alternative to bone marrow (BM) recently has caused important changes on hematopoietic stem cell transplantation (HSCT) practice. According to the CIBMTR data, there has been a significant decrease in the use of bone marrow and increase in the use of PSC and CB as the stem cell source for HSCT performed during 1997–2006 period for patients under the age of 20. On the other hand, the stem cell source in 70% of the HSCT procedures performed for patients over the age of 20 was PSC and the second most preferred stem cell source was bone marrow. CB usage is very limited for the adult population. Primary disease, stage, age, time and urgency of transplantation, HLA match between the patient and the donor, stem cell quantity, and the experience of the transplantation center are some of the associated factors for the selection of the appropriate stem cell source. Unfortunately, there is no prospective randomized study aimed to facilitate the selection of the correct source between CB, PSC, and BM. In this paper, we would like to emphasize the data on stem cell selection in light of the current knowledge for patient populations according to their age and primary disease.

No Significant Benefit of Marrow and Blood HLA-Haploidentical Stem Cell Transplantations Given by Mothers with Long-Term Fetomaternal Microchimerism.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5452-5452
Author(s):  
Ying Wang ◽  
De Pei Wu ◽  
Aining Sun ◽  
Zhengming Jin ◽  
Huiying Qiu
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Chronic Gvhd ◽  
Rank Test ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Standard Intensity ◽  
Significant Difference ◽  
Cell Source

Abstract Non-T-cell-depleted maternal HLA-haploidentical hematopoietic stem cell transplantations(SCT) have been reported feasible based on the hypothesis that long-term fetomaternal microchimerism(FMC) is linked with hyporesponsiveness to inherited paternal antigens(IPAS),but the hypothesis is still in debate due to lack of direct evidence. To determine whether the existence of such microchimerism affect the outcome of maternal HLA-haploidentical SCT, we investigated the outcomes of 18 patients (median age 19) with hematologic malignancies (ALL 8, AML 6, CML 3, NHL 1) who underwent haploidentical SCT from mothers with the same regime from July 2003 to January 2005. Donor was treated with granulocyte colony stimulating factor subcutaneously at a dose of 300μg per day for 5 days before bone marrow harvesting. Leukaphereses were performed using a continuous-flow blood cell separator if CD34+ cells in the bone marrow harvest were less than 4.0×106 cells/kg. Patients with CML or AML in CR received 7.5Gy TBI based standard-intensity regimen combined with cyclophosphamide plus cytarabine. The remaining received non-TBI standard-intensity regimen consisting of cytarabine, busulfan and cyclophosphamide. Antithymocyte globulin(ATG) at a dosage of 2.5mg/kg/day on days −5 to −3 was given as an additional immunosuppressive measure in all patients. To prevent GVHD, patients also received cyclosporin at a dose of 3mg/kg/day as a continuous infusion from day −10, 30mg/kg/day mycophenolate mofetil starting on day −10, and short-term methotrexate administered on days 1, 3, 6, 11 at doses of 15, 10, 10, and 10mg/m2. Among all these patients, microchimerism were confirmed with nested polymerase chain reaction using sequence-specific primers(PCR-SSP) typing for HLA in 10 donor-recipient pairs. In the 2 categories as to whether the microchimeric status of the donor is positive or negative, they had similar characteristics in the background factors such as recipient sex, type of conditioning regime, stem cell source, and disparity of HLA except recipients of positive group had more CML. Engraftment was obtained in all patients. As of august 1, 2005, 5 patients died (1 of relapse, 4 of complication), other 13 patients were alive and free of disease. The 2-year overall survival for the whole cohort was 58%. Although there was a survival advantage for pairs with microchimerism over pairs without it, the influence on outcome was not statistically significant (P=0.9, log-rank test). The cumulative incidences of grade Ò/Ô acute graft-versus-host disease (GVHD) were 39% (95%CI, 17%–64%). Also no significant difference was observed between the two groups. Extensive chronic GVHD developed in 5 of 13 patients who could be evaluated. These results indicate maternal HLA-haploidentical hematopoietic SCT is a acceptable option for patients who lack immediate access to a conventional stem cell source, but the presence of fetomaternal microchimerism may not correlate to the existence of immunological tolerance between mother and offspring.

Pregnancy after Allogeneic Hematopoietic Stem Cell Transplantation in Fanconi Anemia Patients: Multi-Institution Cases Report of Female Fertility Recovery

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 456-456
Author(s):  
Samir Kanaan Nabhan ◽  
Marco Bittencourt ◽  
Michel Duval ◽  
Manuel Abecasis ◽  
Carlo Dufour ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Fanconi Anemia ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Fertility Recovery

Abstract Introduction. Fanconi anemia (FA) is a rare autosomal recessive syndrome characterized by chromosome instability. Main clinical features include progressive bone marrow failure, skeletal defects, increased susceptibility to malignancy and reduced fertility. Moreover, most recipients of allogeneic hematopoietic stem cell transplantation (HSCT) suffer from secondary infertility owing to gonadal damage from myeloablative conditioning. We report a rare clinical situation of FA patients pregnancy after allogeneic HSCT. Methods. Retrospective analysis of transplanted FA female patients from 1982 to 2008. Five centers participated in this study on behalf of Aplastic Anaemia Working Party-EBMT. Medical records were reviewed and data collected on a standard case report form including detailed information on diagnosis, transplant procedure, gynecological and obstetrics follow-up. Results. Among 387 transplanted FA patients we identified 202 females who performed a HSCT with a median age of 10,5 years. Five patients became pregnant after the procedure and one of them, twice. They all had their FA diagnosis confirmed by chromosomal breakage test and a bone marrow aspirate with severe hypoplasia/aplasia. Median age at transplantation was 12 years (range 5–17 years). All patients received myeloablative conditioning regimens (cyclophosphamide with or without thoraco-abdominal irradiation) before a bone marrow transplantation, 4 patients from HLA matched sibling donors and 1 from unrelated donor. During follow-up, 4 patients presented signs of ovarian failure (amenorrhea, low levels of FSH/LH and high levels of estradiol). Apart from 1 patient who spontaneously recovered regular menses, the other three received hormonal replacement therapy (HRT) for this purpose. Pregnancy occurred from 3,5 to 17 years after transplant. One patient had an early interruption with a caesarian section at 27 weeks because of an imminent HELLP syndrome. Other pregnancies were uneventful. Among the newborns, there were no FA positive tests, no congenital anomalies and all of them had normal growth and development. Patients remain alive with a median follow-up of 12 years after transplantation with normal hematological status. Conclusion. Fertility recovery after HSCT can result from incomplete depletion of the ovarian follicle reserve. HRT should begin promptly to prevent the early and late unwanted effects related to oestrogen deficiency after HSCT. Recovery of normal ovarian function and a viable pregnancy, is a realistic possibility even in Fanconi anemia patients following allogeneic SCT.

scholarly journals Impact of graft-versus-host disease prophylaxis on immune reconstitution in patients after allogeneic hematopoietic stem cell transplantation

2021 ◽  
Vol 23 (5) ◽  
pp. 1125-1136
Author(s):  
E. D. Mikhaltsova ◽  
N. N. Popova ◽  
M. Yu. Drokov ◽  
N. M. Kapranov ◽  
Yu. O. Davydova ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Mycophenolate Mofetil ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cyclosporine A ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Gvhd Prophylaxis

The graft-versus-host disease (GVHD) is among the most common complications after hematopoietic stem cell transplantation (allo-HSCT). The main tools for GVHD prevention remain calcineurin inhibitors (cyclosporin A, tacrolimus), methotrexate, mycophenolate mofetil. Upon implementation of reduced-intensity conditioning regimens, antithymocyte globulin was widely introduced. However, negative effects upon reconstitution of T-cell immunity have been noted, thus increasing risk of severe infectious complications and disease relapse. With extended practice of HSCT from alternative (partially matched or haploidentical) donors, cyclophosphamide was increasingly used. Our aim was to study reconstitution of immune cell subpopulations in the patients undergoing bone marrow transplantation (BMT), when using different GVHD prophylaxis regimens, including the schedules with post-transplant CP usage. The study concerned 44 cases classified into 2 groups. The first one included patients with standard immunosuppressive therapy, antithymocyte therapy, cyclosporine A, methotrexate, mycophenolate mofetil. The second group included the patients who received CP as immunosuppressive drug combined with other treatments (cyclosporine A, methotrexate, mycophenolate mofetil). At specified control terms, (D+14, +30, +60, +90) the blood leukocyte subpopulations were assayed by means of multicolor flow cytometry. Absolute counts of CD4+ cells in HSCT recipients treated with CP post-BMT proved to be sufficiently lower at D+14 and +30, than in those treated with classical immunosuppressive therapy. However, at later terms, (D+60, +90), these differences were not observed. Moreover, in CP-treated bone marrow recipients, absolute numbers of CD8+ cells was significantly higher, compared to the patients who received conventional GVHD prophylaxis. Reconstitution of the studied lymphocyte populations in hematopoietic cell recipients did not depend on the GVHD prophylaxis regimen. Usage of CP combined with bone marrow as a source of stem cells, brings about sufficient decrease of some cell populations (CD4+; CD8+; NK cells) at early terms post-transplant. Administration of CP combined with hematopoietic stem cells as the source of hematopoietic graft seems to be more reasonable.

Influence of Human Leukocyte Antigen Haplotypes on Acute Graft Versus Host Disease Incidence after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2887-2887
Author(s):  
Sameer Gupta ◽  
Charu Aggarwal ◽  
Philip L. McCarthy ◽  
Swaminathan Padmanabhan ◽  
Minoo Battiwalla ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Leukocyte ◽  
Hematopoietic Stem ◽  
Hla Alleles ◽  
Leukocyte Antigen ◽  
Graft Versus Host ◽  
Stem Cell Source ◽  
Gvhd Prophylaxis ◽  
Cell Source ◽  
Hla Haplotypes

Abstract There is increasing evidence that the Human Leukocyte Antigen (HLA) alleles may influence the incidence of acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (alloHSCT). Differential presentation of recipient antigens to donor-derived T-cells by the respective HLA molecules may be a responsible factor. We have reported a decreased rate of aGVHD in HLA DR15 positive patients (pt) undergoing alloHSCT for myeloid malignancies (Blood, 2006; 107:1970). We investigated the influence of different HLA alleles and the three most common HLA haplotypes in US Caucasians on grade 2–4 acute GVHD (graded using published criteria) in HLA matched alloHSCT. We conducted a retrospective review of 195 related and 70 unrelated consecutive first myeloablative alloHSCT pt treated from 01/1992 to 4/2005 at our center. HLA typing was determined by either molecular (n=176) or serologic (n=89) methods. Pt characteristics included: AML (n=84), CML (n=62), NHL (n=47), ALL (n=41), MDS (n=20), HD (n=7) and CLL (n=4); median age 39 years (range 6–66), < 40 years (n=130); Male (n=168), Female (n=97); Caucasian (>95%); Donor-Recipient Sex Mismatch (n=112); Total Body Irradiation (TBI) conditioning regimens (n=205); Etoposide/Cyclophosphamide(Cy)/TBI (n=122), Busulfan(Bu)/Cy (n=28), Bu/TBI (n=27), Thiotepa/TBI (n=23), Cy/TBI (n=22), Fludarabine/Melphalan (n=8), Thiotepa/Carboplatin (n=8) or other combinations (n=27) and peripheral blood stem cell source (n= 35). HLA Haplotypes analyzed for their effect on aGVHD were A1B8DR3 (n=25), A3B7DR15 (n=20) and A2B44DR4 (n=13). There was no significant difference in the pt characteristics (donor relation, conditioning regimen, donor-recipient sex match, diagnosis, age, gender, performance status, disease status at transplant, stem cell source and GVHD prophylaxis) by each of the three haplotypes. We analyzed prior published HLA alleles that were associated with an increased or decreased risk of aGVHD and pt characteristics for their effect on grade 2–4 aGVHD incidence. By univariate analysis, donor relation (unrelated vs. related, 52% vs. 38%, p=0.0002), HLA A2 (44% vs. 33%, p=0.05) and HLA B8 were associated with increased aGVHD (61% vs. 37%, p=0.005) whereas HLA B18 was associated with decreased aGVHD (19% vs. 43%, p=0.017) in contrast to prior reports using serological typing only. By multivariate analysis, HLA A2 (RR=1.5, 95%CI: 1.0 to 2.2, p=0.04), HLA B8 (RR=1.9, 95%CI: 1.1 to 3.0, p=0.01) and unrelated donor (RR= 1.9, 95%CI: 1.3 to 2.9, p=0.001) were associated with increased aGVHD. HLA haplotype multivariate analysis demonstrated increased risk of aGVHD with haplotypes A1B8DR3 and A2B44DR4 (A1B8DR3: 64% vs. 32%, RR 2.6, 95% CI: 1.1 to 5.9, p=0.012 and A2B44DR4: 61% vs. 39%, RR 3.5, 95% CI: 1.7 to 7.5, p=0.04) whereas haplotype A3B7DR15 had less aGVHD compared to others (18% vs. 42%, RR 0.31, 95%CI: 0.098 to 0.98, p=0.049). This is the first published report of the effect of HLA haplotypes on aGVHD incidence. Results of our haplotype analysis substantiate our findings of single allele effects of HLA A2, HLA B8 and HLA DR15 suggesting a differential effect on aGVHD incidence. The ability to predict aGVHD after alloHSCT using HLA haplotypes may improve outcomes by allowing for individualized GVHD prophylaxis regimens.

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