scholarly journals Transplantation Using Bone Marrow from a (very) HLA Mismatched Unrelated Donor in the Setting of Post-Transplant Cyclophosphamide Is Feasible and Expands Access to Underserved Minorities

2020 ◽  
Vol 26 (3) ◽  
pp. S283-S284
Author(s):  
Bronwen E. Shaw ◽  
Linda J. Burns ◽  
Brent Logan ◽  
Antonio Martin Jimenez-Jimenez ◽  
Farhad Khimani ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Unrelated Donor ◽  
Post Transplant ◽  
Underserved Minorities

Allogeneic Bone Marrow Transplantation From Unrelated Donors in Multiple Myeloma: A Study from the Italian Bone Marrow Transplantation Donor Registry

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2009-2009
Author(s):  
Benedetto Bruno ◽  
Roberto Passera ◽  
Francesca Patriarca ◽  
Francesca Bonifazi ◽  
Vittorio Montefusco ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Marrow Transplantation ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Unrelated Donor ◽  
Post Transplant ◽  
Stem Cell Source ◽  
Cell Source ◽  
Reduced Intensity

Abstract Abstract 2009 To evaluate the role of allografting from unrelated donors in the treatment of myeloma we conducted a retrospective study through the Italian Bone Marrow Transplantation Donor Registry. Overall, from 2000 through 2009, 196 myeloma patients, median age 51 years (32–67), for a total of 199 allografts, were transplanted from an unrelated donor at 34 Centers in Italy. Fifty-two (28.1%%), 69 (37.3%), and 64 (34.6%) patients were prepared for transplant with a myeloablative, a reduced-intensity and a non-myeloablative conditioning respectively. Patient characteristics of the 3 cohorts are reported in Table 1.ConditioningMyeloablativeReduced-intensityNon-myeloablativePatient number (%)52/185 (28)69/185 (37)64/185 (35)Median Age455355Previous therapy lines < 2 (%)23 (27)33 (38)30 (35)Previous therapy lines ≥ 2 (%)29 (29)36 (37)34 (34)Stem Cell Source BM (%)24 (57)18 (43)0 (0)Stem Cell Source PBSC (%)28 (19)51 (36)64 (45) Cumulative incidence of acute grade II-IV graft-versus-host-disease (GVHD) was 46.4% whereas chronic GVHD was 45.1%. There was no difference in GVHD incidence among the 3 cohorts defined by type of conditioning. Complete and partial remissions in patients who survived at least 3 months post-transplant were 27% and 28% for an overall response rate of 55%. At a median follow up of 32 (0–118) months post-transplant, in the entire study population, median OS from diagnosis was 70.6 months while OS and EFS from the allograft were 18.9 and 14.9 months. Overall, the cumulative incidence of transplant related mortality (TRM) was 29.6% at 1 year and 32.4% at 5 years post-transplant. OS from diagnosis and EFS from transplant were 70.6 and 28.2 months; 66.8 and 9.1 months; and 111.9 and 22.4 months in patients who respectively underwent a myeloablative, a reduced-intensity and a non-myeloablative transplant. One-year and 5-year TRM was 33.3% and 35.7%, 32.2% and 34.4%, and 22.1% and 26.5% respectively. Univariate and multivariate analyses, assessed by multivariate Cox proportional hazards models, were performed for the following variables: number of previous chemotherapy lines (1,2 vs. ≥3), disease status at transplant, HLA- matched antigens (10/10 vs. 9/10 vs. ≤8/10), recipient/donor gender combinations, hematopoietic cell source (peripheral blood vs. bone marrow), conditioning (myeloablative vs. reduced-intensity vs. non-myeloablative), use of anti-thymoglobulin in the conditioning, acute GVHD, chronic GVHD, best response post-transplant, year of transplant (2000–02 vs. 2003–05vs. 2006–09). By univariate analysis, lower number of chemotherapy lines before the allograft, disease status at transplant, a fully HLA-identical donor, the use of peripheral hematopoietic cells rather than bone marrow were statistically significant variables for better OS whereas disease status at transplant, a fully HLA-identical donor, chronic GVHD (either limited or extensive) were statistically significant for better EFS. However, by multivariate analysis, only the development of chronic GVHD (HR 0.50; p<0.001) and a better response post-transplant (HR 2.11; p<0.03) were significantly associated with longer OS whereas chronic GVHD was the only variable associated with better EFS (HR 0.32; p<0.001). Acute GVHD was associated with both poorer OS (HR 2.35; p<0.001)) and EFS (HR 3.19; p<0.001). In conclusion, with a degree of caution given the retrospective nature of this study, there appears to be a strong association between both limited and extensive chronic GVHD and graft-vs.-myeloma effects. However, long term disease control remains an issue independent of the conditioning employed. Prospective trials may allow to define which patient category may most benefit from an unrelated donor allograft. Disclosures: Patriarca: Roche: Honoraria; Celgene: Honoraria; Schering-Plough: Honoraria; Janssen: Honoraria. Boccadoro:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Favorable Results of Allo-HSCT from MRD in Patients with Myelofibrosis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5934-5934
Author(s):  
Miroslaw Markiewicz ◽  
Monika Dzierzak-Mietla ◽  
Patrycja Zielinska ◽  
Agata Wieczorkiewicz-Kabut ◽  
Sylwia Mizia ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Collagen Type ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Graft Loss ◽  
Chronic Phase ◽  
Curative Treatment ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Post Transplant

Abstract Introduction: Myelofibrosis (MF), chronic myeloid malignancy associated with shortened survival, in majority of patients develops de novo as Primary MF, but also polycythemia vera (PV) or essential thrombocythemia (ET) may progress into post-PV or post-ET MF. Although management of MF includes several treatment options, the only potentially curative treatment approach in MF is allogeneic hematopoietic stem cell transplantation (allo-HSCT). Aim of this study was to evaluate the results of allo-HSCT in patients with MF treated in Katowice, Poland. Material and Methods: 27 pts (14 male and 13 female) with median age 51 years (range 21–63) were treated with allo-HCT due to PMF (20), post-PV (4) or post-ET (3) MF. 11,7,11,26 and 41% of pts had DIPSS 0,1,2,3 and 4, respectively. Median bone marrow cellularity was 70% (10-100%), fibrosis was collagen-type (14 pts including 2 with osteosclerosis), reticulin (10) or it was not specified (3). Splenomegaly was present in all pts: 13-20 cm (14 pts), > 20 cm (13 pts). JAK2V617F point mutation was present in 18 pts. Karyotype was available in 14 pts: in 9 normal, in 5 with variable abnormalities. Median time from diagnosis to allo-HCT was 1.5 (0.4–9.5) years. 16 pts (59.3%) received cells from HLA-matched related donor (MRD), 11 pts (40.7%) from unrelated donor: 10/10 (9) or 9/10 (2) HLA-A,B,C,DR,DQ alleles matched. Reduced intensity conditioning (RIC) was used in 26 pts, 1 patient received myeloablative conditioning (MC). Sources of stem cells were: peripheral blood (21), bone marrow (4) and both (2). All pts but one had chronic phase of MF at time of transplantation. Results: 14/27 (52%) pts are alive at median 3.4 (0.4-5.4) years after allo-HSCT: 11/16(69%) from MRD and 3/11(27%) from MUD, p=0.032. Graft failure, graft loss or PRCA were observed in 3, 5 and 1 pt, respectively. Absolute neutrophil count >0.5×109/L and platelet count >50×109/L were achieved at median 16 and 28 days, respectively. 12/27 (44%) pts reached complete blood count of Hb>10 g/dl, Plt>100 G/l and WBC>3.5 G/l; 11 of them (92%) are alive. 6/27 (22%) pts remained either RBC or PLT transfusions dependent post-transplant; 3 of them (50%) died. 9/27 (33%) pts remained both RBC and PLT transfusion dependent and all of them died. JAK2V617F mutation was completely eradicated in 11/16 evaluated previously positive patients (69%), decreased in 4 (25%) and stable in 1(6%) pt. Acute graft-versus-host disease (aGVHD) III-IV developed in 5/27 (19%) and extensive chronic GVHD in 5/19 (26%) pts. Relapse occurred in 4 pts and was treated with subsequent second transplant (in 1 pt thereafter by 3-rd allo-HSCT). Spleen length decreased at median by 5 (0.3-9.2) cm. Out of 7 pts with initial collagen fibrosis who were evaluated post-transplant, 1 had no fibrosis, 5 reticulin type and only in 1 pt collagen fibrosis was stable. Out of 3 pts with initial reticulin fibrosis it disappeared in 2 and progressed to collagen type in 1. Causes of death were GVHD (5 pts: 3 aGVHD, 2 cGVHD) and pancytopenia with either infection (7 pts) or CNS hemorrhage (1 pt). Conclusions: Allo-HSCT, the only curative treatment of myelofibrosis, provides chance of long survival, regression of the disease (lower stage of fibrosis, JAK2V617F eradication) and improved quality of life (transfusion independency, decreased splenomegaly). Transfusion independency may indicate good outcome. Favorable results are observed after allo-HSCT from MRD. Disclosures No relevant conflicts of interest to declare.

EBV Related Lymphoproliferative Disorders Post Allogeneic Bone Marrow Transplantation for Haematological Malignancies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5480-5480
Author(s):  
A. Paisiou ◽  
C. M. Vadikolia ◽  
K. Stefanaki ◽  
E. Goussetis ◽  
I. Peristeri ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Allogeneic Bone Marrow Transplantation ◽  
Unrelated Donor ◽  
Allogeneic Bone ◽  
Haematological Malignancies ◽  
Hla Antigen ◽  
Post Transplant ◽  
Concurrent Infections

Abstract Background: Post transplant lymphoproliferative disorder (PTLD) is a heterogeneous complication of HSCT. It comprises a spectrum of pathogenetic mechanisms and clinical manifestations. It is mostly associated with EBV infection, either as a consequence of reactivation in the post transplant period or less frequently from primary infection. WHO classification defines four major histopathologic subtypes: 1. early plasmacytic hyperplasia and infectious mononucleosis (IM)-like 2. polymorphic lesions which may be polyclonal or focally monoclonal (P-PTLD) 3. monomorphic lesions that fulfill criteria for aggressive B- or T/NL-cell neoplasm (M-PTLD) 4. classic Hodgkin-type Lymphomas (CHL-PTLD). Indistinguishable categories, such as Hodgkin-like P-or M-PTLD might represent laborious diagnostic dilemmas. In literature, PTLD occurs in less than 1% of non T-cell-depleted grafts from matched siblings compared with as high as 25% in unrelated donor (VUD) recipients. There are several risk factors such as the type of conditioning and the use of ATG, the degree of immunosuppression and complications such as concurrent infections and GvHD. Objectives: To present our experience regarding the frequency, presentation and outcome of EBV related PTLD in a paediatric population of allo-HSCT recipients with haematological malignancies, to assess the risk factors and inquire into the heterogeneity in clinical presentation and outcome. Patients-Methods: From January 2004 until December 2014, 177 allo-HSCTs for myeloid and lymphoid malignancies were performed in patients aged 3 months to 19 years. PTLD was recorded in 15 (8 male) with median age of 13.24 yrs (range 5.0-17.9yrs). 11 patients had VUD, 4 patients had an haploidentical related donor and the grafts depleted of T-cells. 12 patients had peripheral blood and 3 had bone marrow as the source of HSCs. 4 were given a fully matched graft, 6 had 1 HLA antigen or allele mismatched donors, 1 patient had a 2 HLA antigen mismatched donor and 4 had 5/10 HLA matched haploidentical donors. All except for 2 patients were EBV IgG positive and the two seronegative patients had an EBV IgG positive donor. The conditioning regimens used were Busulfan or Treosulfan based in 11 patients with the addition of a combination of Cyclophosphamide, Fludarabine, Melphalan, VP16 and ATG. The latter was administered to all patients. GvHD prophylaxis consisted of Cyclosporin A and Methotrexate. Five patients (1 male) are alive and well with a median follow up of 43.1 months (range 8.3-69.2). Results: Neutrophil and platelet engraftment occurred at a median of 20 (range 14-24) and 21 days (range 14-48) respectively. Acute GvHD (stage II-IV) was recorded in 9 patients. Serial quantitative EBV-DNA/ml was employed routinely and the median day of confirmation of a rising level above 1.0x103/ml was day +58 post transplant. Median EBV copies at diagnosis were 2.3x104/ml(range 1.3x103/ml-2.15x105/ml). EBV positivity was immediately recorded post DLI in 3 patients and reactivation occurred post subsequent DLI. Immune reconstitution had not been achieved in any patient at the time of diagnosis. Median WBC count was 4.1x109/lt (1.04X109/lt - 8.78x109/lt) and all patients had absolute lymphopenia. 9 patients had documented other viral and/or bacterial infections. 2 patients developed M-PTLD, consistent unequivocally with DLBCL, 7 patients had P-PTLD and 6 patients had IM-like PTLD with plasmacytic hyperplasia only. All had anti-CD20, two patients had additional chemotherapy. Although responsive to EBV treatment, 3 died of primary disease recurrence while PTLD failed to regress in 7 patients who died of a multitude of complications. With a median follow up of 43,1 months (range 8.3-69.2), 5 patients (1 male) are alive and well. Conclusions: Nearly all HSCT recipients are EBV infected or will be infected eventually, yet only a fraction develop EBV driven PTLD. In our population the incidence was found to be 8.47%. PTLD exhibits a spectrum of features ranging from non specific and reactive to life threatening, indistinguishable from lymphoma. Administration of ATG, the type and extend of HLA mismatch, multiple sites of disease, immune suppression and concurrent infections heighten the risk of systemic manifestation. Rising EBV loads are strongly associated with impending PTLD, which can occur even with an overall modest viral load, thus requiring prompt recognition and early intervention. Disclosures No relevant conflicts of interest to declare.

National Marrow Donor Program–Sponsored Multicenter, Phase II Trial of HLA-Mismatched Unrelated Donor Bone Marrow Transplantation Using Post-Transplant Cyclophosphamide

2021 ◽  
pp. JCO.20.03502
Author(s):  
Bronwen E. Shaw ◽  
Antonio Martin Jimenez-Jimenez ◽  
Linda J. Burns ◽  
Brent R. Logan ◽  
Farhad Khimani ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase Ii ◽  
Hematopoietic Cell Transplantation ◽  
Unrelated Donor ◽  
Minority Population ◽  
Reduced Intensity Conditioning ◽  
Entire Cohort ◽  
Post Transplant ◽  
End Point ◽  
Reduced Intensity

PURPOSE Hematopoietic cell transplantation (HCT) is curative for hematologic disorders, but outcomes are historically inferior when using HLA-mismatched donors. Despite unrelated donor registries listing > 38 million volunteers, 25%-80% of US patients lack an HLA-matched unrelated donor, with significant disparity across ethnic groups. We hypothesized that HCT with a mismatched unrelated donor (MMUD) using post-transplant cyclophosphamide (PTCy), a novel strategy successful in overcoming genetic disparity using mismatched related donors, would be feasible and increase access to HCT. PATIENTS AND METHODS We performed a prospective phase II study of MMUD bone marrow HCT with PTCy for patients with hematologic malignancies. The primary end point was 1-year overall survival (OS), hypothesized to be 65% or better. 80 patients enrolled at 11 US transplant centers (December 2016-March 2019). Following myeloablative or reduced-intensity conditioning–based HCT, patients received PTCy on days +3, +4, with sirolimus and mycophenolate mofetil starting on day +5. We compared outcomes to Center for International Blood and Marrow Transplant Research contemporary controls receiving PTCy. RESULTS Notably, 48% of patients enrolled were ethnic minorities. 39% of pairs were matched for 4-6 out of 8 HLA alleles. The primary end point was met, with 1-year OS of 76% (90% CI, 67.3 to 83.3) in the entire cohort, and 72% and 79% in the myeloablative and reduced-intensity conditioning strata, respectively. Secondary end points related to engraftment and graft-versus-host-disease were reached. Multivariate analysis comparing the study group with other mismatched HCT controls found no significant differences in OS. CONCLUSION Our prospective study demonstrates the feasibility and effectiveness of HCT with an MMUD in the setting of PTCy. Remarkably, nearly half of the study participants belonged to an ethnic minority population, suggesting this approach may significantly expand access to HCT.

scholarly journals Haploidentical Stem Cell Transplantation with Post-Transplant Cyclophosphamide As Graft-Versus-Host Disease Prophylaxis in Pediatric Hematologic Malignancies

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5705-5705
Author(s):  
Gerardo Lopez-Hernandez ◽  
Norma Lopez-Santiago ◽  
Alberto Olaya-Vargas ◽  
Martín Pérez-García ◽  
Rosa María Nideshda Ramírez-Uribe ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Pediatric Patients ◽  
Hematologic Malignancies ◽  
Marrow Transplant ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Post Transplant

Abstract Background Hematopoietic stem cell transplantation (HSCT) is used in pediatric patients with acute leukemia, after a relapse to bone marrow, or in first remission in case of high risk disease. If necessary, 75% of the cases do not have a compatible related donor and it is not always possible to have a compatible unrelated donor or an umbilical cord blood unit. Therefore, using haploidentical alternative donors of hematopoietic stem cells (HSC) is becoming more frequent. Objective The purpose of this is to report the results of haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide (PTCy) in a group of pediatric patients, which lacks a related HLA compatible donor, at the National Pediatrics Institute in México City, México, in the period between January 2012 thru December 2016. Methods We retrospectively reviewed 27 patients´ files <18 years old, who had been diagnosed with acute lymphoblastic leukemia (ALL, eighteen patients), or acute myeloid leukemia (AML, nine patients), and underwent on haploidentical transplantation with post-transplant cyclophosphamide (PTCy). The group of patients consisted of eighteen men and nine women. Age ranged from one to eighteen years (median age eight years). Sixteen patients were in their first hematologic remission, eight in their second, two in their third and one in their fourth hematologic remission, respectively. All donors were ⩾ 4 HLA loci mismatched parents (mother, n = 17; father, n = 8), or siblings, n = 2. Conditioning was based on a nonmyeloablative regimen comprised of fludarabine 50 mg/m2, days -6 to -2, cyclophosphamide 14.5 mg/kg, days -6 and -5, and low-dose total body irradiation 200 cGy at day -1. Graft versus host disease prophylaxis comprised Cy 50 mg/kg intravenous on day 3 and 4 after transplantation, followed by tacrolimus 0.06 mg/kg and mycophenolate mofetil 15 mg/kg, each beginning on day 5. According to the availability of bone marrow harvesting kit, the HSC source was peripheral blood in twenty patients and bone marrow in seven. The median number of CD34+ cells infused was 5.41 × 106/kg (range, 1.27-22.6). Results Fourteen patients (51.6%) presented complete and sustained chimerism. Overall survival is presented in Figure 1. Graft failure occurred (48.1%) more frequently in the group of patients in whom bone marrow was used as a source of HSC (p=0.26). Nine patients with complete chimera, whose HSC source turned out to be PB, presented acute-GVHD III-IV (p = 0.06). Four of the patients whom presented full engraftment died, three of them due to infectious processes (cytomegalovirus pneumonia, AH1N1 pneumonia, abdominal sepsis secondary to intestinal perforation and E. coli sepsis), before +100-day post-transplantation. All these patients presented acute-GVHD III-IV. The fourth patient who died, also the cause was infectious (pulmonary sepsis secondary to Morganella morganii), thirteen months after the transplant and without history of GVHD. Of the thirteen patients who presented primary graft failure, seven of them are alive and without evidence of tumoral activity Discussion Haploidentical transplantation with PTCy is a feasible therapeutic option in pediatric patients with malignant hematological diseases who require a HSCT and do not have a matched sibling or unrelated donor available. Conflict-of-interest disclosure: The authors declare they have nothing to disclose. Correspondence: Gerardo López-Hernández. [email protected] BibliographyKlein OR, Buddenbaum J, Tucker N, et al. Nonmyeloablative Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide for Pediatric and Young Adult Patients with High-Risk Hematologic Malignancies. Biol Blood Marrow Transplant. 2017; 23(2): 325-332.González-Llano O, González-López EE, Ramírez-Cázares AC, et al. Haploidentical peripheral blood stem cell transplantation with posttransplant cyclophosphamide in children and adolescents with hematological malignancies. Pediatr Blood Cancer. 2016; 63: 2033-2037.Robinson TM, O'Donnell PV, Fuchs EJ, Luznik L. Haploidentical bone marrow and stem cell transplantation: experience with post-transplantation cyclophosphamide. Semin Hematol. 2016; 53(2): 90-97.Fuchs EJ, Huang XJ, Miller JS. HLA-haploidentical stem cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant. Biol Blood Marrow Transplant. 2010; 16 (1 Suppl): S57-S63. Disclosures No relevant conflicts of interest to declare.

Chronic GVHD Is Not Increased with the Use of PBSC Instead of Bone Marrow for T-Replete HLA-Haploidentical Transplanation Using Post-Transplant Cyclophosphamide : A Multivartiate Analysis of 116 Consecutive Transplants from a Single Center

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3922-3922
Author(s):  
Asad Bashey ◽  
Xu Zhang ◽  
Stacey Brown ◽  
Katelin Connor ◽  
Lawrence E. Morris ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multivariate Analysis ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
Cox Model ◽  
Risk Index ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Post Transplant ◽  
Increased Risk

Abstract HLA-haploidentical related donors (HID) are a potential option for patients who need an allogeneic haploidentical transplant but lack an optimally matched conventional donor (HLA-identical sibling or 8 of 8 HLA-A, B, C, DRB1 matched unrelated donor) (MRD and MUD respectively). The Baltimore approach to HID transplantation that uses T-replete grafts and post-transplant cyclophosphamide to control alloreactivity (HIDT-ptCy) has demonstrated promising outcomes and appears to be safe and effective. Bone marrow (BM) grafts have almost exclusively been used for HIDT-ptCy in Baltimore. Early studies from other centers have demonstrated that G-CSF mobilized PBSC may be safely used for HIDT-ptCy (Castagna et al BBMT 2014, Raj et al BBMT 2014). HIDT-ptCy using BM grafts has been associated with relatively low rates and severity of chronic GVHD. However, it is unclear whether the use of PBSC for HIDT-ptCy will be associated with higher rates of chronic GVHD than with BM grafts as has been demonstrated for MRD and MUD transplants. We analyzed 116 consecutive HIDT-ptCy first transplants (BM=64, PBSC=52) performed for hematologic malignancies at our center. Identical supportive care measures were utilized for BM and PBSC patients. GVHD was prospectively documented using established criteria by a single dedicated nurse. NIH consensus criteria were used for chronic GVHD. Gray's test was used to compare the cumulative incidences of GVHD. A Cox model was used in multivariate analysis of GVHD outcomes. Characteristics of the patients are demonstrated in Table 1. Patients undergoing HIDT-ptCy using PBSC were significantly more likely to receive myeloablative conditioning, were younger, were less likely to have been transplanted prior to 2007. Although the frequency of diagnoses differed, the Dana-Farber/CIBMTR Disease Risk Index (DRI) was not significantly different between the two groups. Median follow-up for BM and PBSC patients was 44 m and 25 m. Six month cumulative incidences of acute GVHD grades 2-4 were 39% and 42% and grades 3-4 were 14% and 21% for BM and PBSC grafts respectively. The two year cumulative incidences of extensive chronic GVHD were 38% and 45% and for severe chronic GVHD were 8% and 6% respectively (p=NS for all BM vs PBSC comparisons). In a multivariate analysis assessing effects of patient, disease and transplant variables on GVHD outcomes, graft type i.e. PBSC vs BM was not a significant predictive factor for acute or chronic GVHD. These data demonstrate that unlike the case following MRDT and MUDT, G-CSF mobilized PBSC grafts are not associated with an increased risk of chronic GVHD than BM grafts following HIDT-ptCy. Severe chronic GVHD is very uncommon with both types of graft following HIDT-ptCy and is an indication of the effectiveness of ptCy in controlling alloreactivity in this setting. Disclosures No relevant conflicts of interest to declare.

scholarly journals Donor Recipient Chimeric Cells Induce Chimerism and Extend Survival of Vascularized Composite Allografts

2021 ◽  
Vol 69 (1) ◽  
Author(s):  
Joanna Cwykiel ◽  
Arkadiusz Jundzill ◽  
Aleksandra Klimczak ◽  
Maria Madajka-Niemeyer ◽  
Maria Siemionow
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Fluorescent Microscopy ◽  
Study Endpoint ◽  
Solid Organ ◽  
Post Transplant ◽  
Group 4 ◽  
Cell Based Therapy ◽  
Group 3 ◽  
Group 1

AbstractThis study evaluated the efficacy of donor recipient chimeric cell (DRCC) therapy created by fusion of donor and recipient derived bone marrow cells (BMC) in chimerism and tolerance induction in a rat vascularized composite allograft (VCA) model. Twenty-four VCA (groin flaps) from MHC-mismatched ACI (RT1a) donors were transplanted to Lewis (RT1l) recipients. Rats were randomly divided into (n = 6/group): Group 1—untreated controls, Groups 2—7-day immunosuppression controls, Group 3—DRCC, and Group 4—DRCC with 7-day anti-αβTCR monoclonal antibody and cyclosporine A protocol. DRCC created by polyethylene glycol-mediated fusion of ACI and Lewis BMC were cultured and transplanted (2–4 × 106) to VCA recipients via intraosseous delivery route. Flow cytometry assessed peripheral blood chimerism while fluorescent microscopy and PCR tested the presence of DRCC in the recipient’s blood, bone marrow (BM), and lymphoid organs at the study endpoint (VCA rejection). No complications were observed after DRCC intraosseous delivery. Group 4 presented the longest average VCA survival (79.3 ± 30.9 days) followed by Group 2 (53.3 ± 13.6 days), Group 3 (18 ± 7.5 days), and Group 1 (8.5 ± 1 days). The highest chimerism level was detected in Group 4 (57.9 ± 6.2%) at day 7 post-transplant. The chimerism declined at day 21 post-transplant and remained at 10% level during the entire follow-up period. Single dose of DRCC therapy induced long-term multilineage chimerism and extended VCA survival. DRCC introduces a novel concept of customized donor-recipient cell-based therapy supporting solid organ and VCA transplants.

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