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1.
HLA ; 103(6): e15560, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38839559

ABSTRACT

De novo anti-HLA donor-specific antibodies (DSAs) were rarely reported in stem cell transplantation patients. We present a case of 39-year-old acute myelogenous leukaemia patient who developed de novo DSAs only 16 days after transplantation with the highest mean fluorescence intensity (MFI) of 7406.23, which were associated with poor graft function (PGF). We used plasma exchange (PE) and intravenous immunoglobulin (IVIg) to reduce DSA level. A series of treatment including mesenchymal stem cells and donor cell transfusion were used to help recover graft function. On day 130, the patient achieved a successful engraftment.


Subject(s)
HLA Antigens , Hematopoietic Stem Cell Transplantation , Isoantibodies , Leukemia, Myeloid, Acute , Humans , Hematopoietic Stem Cell Transplantation/methods , Adult , HLA Antigens/immunology , Isoantibodies/immunology , Isoantibodies/blood , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/immunology , Male , Tissue Donors , Transplantation, Haploidentical/methods , Immunoglobulins, Intravenous/therapeutic use , Plasma Exchange/methods , Female , Histocompatibility Testing
2.
Leuk Res ; 143: 107530, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38852515

ABSTRACT

Primary graft failure (PGF) and multi-lineage cytopenia (MLC) increase the risk of nonrelapse mortality in allogeneic hematopoietic cell transplants (HCT). We evaluated the impact of post-transplant cyclophosphamide (PTCy) and splenomegaly on PGF and MLC for hematological malignancies. This study included patients with PTCy (N=84) and conventional graft-vs.-host disease prophylaxis (N=199). The occurrence of splenomegaly varied widely, ranging from 17.1 % (acute myeloid leukemia) to 66.7 % (myeloproliferative neoplasms). Ten patients (N=8 in the PTCy and N=2 in the non- PTCy) developed PGF, and 44 patients developed MLC (both N=22). PTCy and severe splenomegaly (≥20 cm) were risk factors for PGF (odds ratio (OR): 10.40, p<0.01 and 6.74, p=0.01 respectively). Moreover, severe splenomegaly was a risk factor for PGF in PTCy patients (OR: 10.20, p=0.01). PTCy (hazard ratio (HR) 2.09, p=0.02), moderate (≥15, <20 cm, HR 4.36, p<0.01), and severe splenomegaly (HR 3.04, p=0.01) were independent risk factors for MLC. However, in subgroup analysis in PTCy patients, only mild splenomegaly (≥12, <15 cm, HR 4.62, p=0.01) was a risk factor for MLC. We recommend all patients be screened for splenomegaly before HCT, and PTCy is cautioned in those with splenomegaly.

3.
Front Pediatr ; 12: 1375493, 2024.
Article in English | MEDLINE | ID: mdl-38783918

ABSTRACT

Objectives: To describe mesenchymal stromal cells (MSCs) in the treatment of hematopoietic stem cell transplantation (HSCT) complications and to assess its safety and efficacy. Methods: Single-center retrospective study (2016-2023). Patients under 20 years who received MSCs for the treatment of HSCT-related complications were included. Results: Thirty patients (53.7% boys), median age at transplant 11 years (range 2-19) were included. MSCs indications were: graft-vs.-host disease (GVHD) in 18 patients (60%), of them 13 had acute GVHD (43.3%) and 5 chronic GVHD (16.7%); Grade 3-4 hemorrhagic cystitis (HC) in 4 (13.3%); poor graft function (PGF) in 6 (20%), 5 of them receiving MSCs with a CD34 stem cell-boost coinfusion; graft failure (GF) in 2 (6.7%), to enhance engraftment after a subsequent HSCT. Infusion-related-adverse-events were not reported. Overall response (OR) was 83% (25/30); 44% of responders (11/25) showed complete response (CR). OR for GVHD, HC, PGF and GF was 83.3%, 100%, 66.7% and 100% respectively. Response rate was 40% (95% CI: 20-55) and 79% (95% CI: 57-89) at 15 and 30 days. With a median follow-up of 21 months (IQR11-52.5), overall survival (OS) was 86% (95% CI: 74-100) and 79% (95% CI: 65-95) at 6 and 12 months post-MSCs infusion. Conclusion: In our study, the most frequent indication of MSCs was refractory aGVHD (43.3%). Response rates were high (OR 83%) and safety profile was good.

4.
Perioper Med (Lond) ; 13(1): 11, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38419073

ABSTRACT

INTRODUCTION: Initial allograft function determines the patient's immediate prognosis in pediatric liver transplantation. Ischemia-reperfusion injuries play a role in initial poor graft function (IPGF). In animal studies, preconditioning with inhaled anesthetic agents has demonstrated a protective effect on the liver. In humans, the few available studies are conflicting. This study assesses the association between the hypnotic agent used to maintain anesthesia during hepatectomy in living donors and the occurrence of IPGF after pediatric transplantation. METHODS: We conducted a single-center retrospective analysis of children who received a living donor liver transplant (LDLT) between 2010 and 2019. We analyzed the incidence of EAD according to the hypnotic agent used to maintain general anesthesia during donor hepatectomy. RESULTS: We included 183 pairs of patients (living donors-recipients). The anesthetics used in the donor were propofol (n = 85), sevoflurane (n = 69), or propofol with sevoflurane started 30 min before clamping (n = 29). Forty-two children (23%) developed IPGF. After multivariate logistic regression analysis, factors significantly associated with the occurrence of IPGF were the anesthesia maintenance agent used in the donor (p = 0.004), age of the donor (p = 0.03), duration of transplant surgery (p = 0.009), preoperative receiver neutrophil to lymphocyte ratio (p = 0.02), and albumin (p = 0.05). CONCLUSION: Significantly fewer children who received a graft from a donor in whom only sevoflurane was used to maintain anesthesia developed IPGF. Although additional research is needed, this preconditioning strategy may provide an option to prevent IPGF after living liver donation.

5.
Cureus ; 15(9): e44555, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37790070

ABSTRACT

INTRODUCTION: Allogeneic stem cell transplantation (ASCT) is a crucial therapeutic strategy for hematological and non-hematological disorders. Poor graft function (PGF) after ASCT presents a critical challenge that does not have a standardized treatment approach. A thrombopoietin-mimetic oral drug eltrombopag shows promise in some bone failure syndromes. This study aimed to analyze the efficacy of eltrombopag in treating PGF after ASCT. METHODS: Patients receiving eltrombopag for PGF after ASCT between 2017 and 2020 were retrospectively evaluated. Patients' characteristics, details for ASCT, timing, treatment, and possible contributors for PGF, response to eltrombopag treatment, and overall response rate (ORR) were analyzed.  Results: Eighteen patients were assessed. Eltrombopag treatment yielded a favorable response in 11 patients, resulting in an ORR of 61%. The ORR in secondary PGF was better than that in primary PGF (83% and 17% respectively). There was a marked enhancement in platelet and hemoglobin levels following eltrombopag treatment (p=0.001 and p=0.030, respectively), while neutrophil values exhibited no significant change (p=0.8). Among the responding patients, four individuals (22%) underwent a tapering and discontinuation of eltrombopag. No toxicity was observed above grade one, and no patient discontinued eltrombopag because of intolerability or adverse events. CONCLUSION: Our findings affirm that eltrombopag can treat poor graft function after allogeneic stem cell transplantation without significant toxicities. These results contribute to the growing body of evidence supporting the use of eltrombopag in poor graft function after allogeneic stem cell transplantation, providing insights into its potential benefits and limitations.

6.
Front Immunol ; 14: 1213560, 2023.
Article in English | MEDLINE | ID: mdl-37818364

ABSTRACT

Poor graft function (PGF), manifested by multilineage cytopenias and complete donor chimerism post-allogeneic stem cell transplantation (alloSCT), and acquired aplastic anaemia (AA) are immune-mediated acquired bone marrow (BM) failure syndromes with a similar clinical presentation. In this study, we used spatial proteomics to compare the immunobiology of the BM microenvironment and identify common mechanisms of immune dysregulation under these conditions. Archival BM trephines from patients exhibited downregulation of the immunoregulatory protein VISTA and the M2 macrophage marker and suppressor of T-cell activation ARG1 with increased expression of the immune checkpoint B7-H3 compared to normal controls. Increased CD163 and CD14 expression suggested monocyte/macrophage skewing, which, combined with dysregulation of STING and VISTA, is indicative of an environment of reduced immunoregulation resulting in the profound suppression of hematopoiesis in these two conditions. There were no changes in the immune microenvironment between paired diagnostic AA and secondary MDS/AML samples suggesting that leukaemic clones develop in the impaired immune microenvironment of AA without the need for further alterations. Of the eight proteins with dysregulated expression shared by diagnostic AA and PGF, the diagnostic AA samples had a greater fold change in expression than PGF, suggesting that these diseases represent a spectrum of immune dysregulation. Unexpectedly, analysis of samples from patients with good graft function post-alloSCT demonstrated significant changes in the immune microenvironment compared to normal controls, with downregulation of CD44, STING, VISTA, and ARG1, suggesting that recovery of multilineage haematopoiesis post-alloSCT does not reflect recovery of immune function and may prime patients for the development of PGF upon further inflammatory insult. The demonstrable similarities in the immunopathology of AA and PGF will allow the design of clinical interventions that include both patient cohorts to accelerate therapeutic discovery and translation.


Subject(s)
Anemia, Aplastic , Hematopoietic Stem Cell Transplantation , Pancytopenia , Humans , Proteomics , Bone Marrow , Bone Marrow Failure Disorders , Anemia, Aplastic/metabolism
7.
Ann Hematol ; 102(6): 1561-1567, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37083956

ABSTRACT

This is a retrospective cohort study of consecutive adult patients who received a haploidentical-SCT (haplo-SCT) with post-transplant cyclophosphamide (PT-Cy) in a single centre. Poor graft function (PGF) was defined as the occurrence of either persistent neutropenia (ANC < 0.5 × 109/µL) with poor response to granulocyte colony-stimulating factors (G-CSF) and/or thrombocytopenia (platelets < 20 × 109/L) with transfusion dependence, with complete donor chimerism and without concurrent severe GVHD or underlying disease relapse, during the first 12 months after transplantation. Forty-four (27.5%) out of 161 patients were diagnosed with PGF. Previous CMV reactivation was significantly more frequent in patients with PGF (88.6% versus 73.5%, p = 0.04) and the number of reactivations was also higher in these patients. Besides, early CMV reactivations in the first 6 months post-SCT were also significantly more frequent among patients with PGF (88.6% versus 71.8% p = 0.025). Thirty-two percent of patients with PGF were treated with increasing doses of thrombopoietin-receptor agonists (TRA) and 7 patients were treated with a donor CD34 + selected boost. In total, 93.2% of patients reached adequate peripheral blood counts in a median time of 101 days (range 11-475) after diagnosis. PGF is a frequent complication after haplo-SCT with PT-Cy. CMV reactivation might be the most relevant factor associated to its development. Even when most patients recover peripheral counts with support therapy, there is a group of patients with persistent cytopenias who can effectively be treated with TRA and/or a boost of CD34 + selective cells.


Subject(s)
Cytomegalovirus Infections , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Adult , Humans , Retrospective Studies , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Cyclophosphamide/therapeutic use , Cytomegalovirus Infections/complications , Transplantation Conditioning/adverse effects
8.
Front Pediatr ; 11: 1099372, 2023.
Article in English | MEDLINE | ID: mdl-36873638

ABSTRACT

Thrombocytopenia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a common and life-threatening complication. Thus, new prevention and treatment strategies for post-HSCT thrombocytopenia are urgently required. In recent studies, thrombopoietin receptor agonists (TPO-RA) for treating post-HSCT thrombocytopenia indicated efficiency and safety. The improved effect of post-HSCT thrombocytopenia in adults was found in the administration of avatrombopag which was a new TPO-RA. However, there was no relevant study in the children's cohort. Herein, we retrospectively analyzed the effect of avatrombopag in post-HSCT thrombocytopenia in children. As a result, the overall response rate (ORR) and complete response rate (CRR) were 91% and 78%, respectively. Furthermore, both cumulative ORR and CRR were significantly lower in the poor graft function (PGF)/secondary failure of platelet recovery (SFPR) group compared to the engraftment-promotion group (86.7% vs. 100%, p = 0.002 and 65.0% vs. 100%, p < 0.001, respectively). Achieving OR required a median of 16 days in the PGF/SFPR group while 7 days in the engraftment-promotion group (p = 0.003). Grade III-IV acute graft vs. host disease and inadequate megakaryocytes were identified as risk factors of CRR only in univariate analysis (p = 0.03 and p = 0.01, respectively). No severe adverse events were documented. Conclusively, avatrombopag is an alternatively efficient and safe agent for treating post-HSCT thrombocytopenia in children.

9.
Blood Rev ; 60: 101076, 2023 07.
Article in English | MEDLINE | ID: mdl-36990959

ABSTRACT

Poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (HCT) is a serious complication with high morbidity and mortality. The reported incidence of PGF, its risk factors and outcome vary substantially between studies. This variability may be explained by heterogeneity in patient cohorts and HCT strategies, differences in the underlying causes of cytopenia, as well as by differences in PGF definition. In this systematic review and meta-analysis, we provide an overview of the various PGF definitions used and determined the impact of this variability on the reported incidence and outcome. We searched MEDLINE, EMBASE and Web of Science up to July 2022, for any study on PGF in HCT recipients. We performed random-effect meta-analyses for incidence and outcome and subgroup analyses based on different PGF criteria. Among 69 included studies (14.265 HCT recipients), we found 63 different PGF definitions, using various combinations of 11 common criteria. The median incidence of PGF was 7% (IQR: 5-11%, 22 cohorts). The pooled survival of PGF patients was 53% (95% CI: 45-61%, 23 cohorts). The most commonly reported risk factors associated with PGF were history of cytomegalovirus infection and prior graft-versus-host disease. Incidence was lower in studies with strict cytopenic cutoffs, while survival was lower for primary compared to secondary PGF. This work indicates that a standardized, quantitative definition of PGF is needed to facilitate clinical guideline development and to advance scientific progress.


Subject(s)
Cytomegalovirus Infections , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Incidence , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/diagnosis , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Cytomegalovirus Infections/etiology , Risk Factors
10.
Br J Haematol ; 201(6): 1153-1158, 2023 06.
Article in English | MEDLINE | ID: mdl-36974355

ABSTRACT

Haematopoietic stem cell reinjection may be a curative option for poor graft function after haematopoietic stem cell transplantation; however, literature supporting its use remains limited. We conducted a multicentre retrospective study on behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy, including 55 patients. We demonstrated response rates of nearly 40% and two-year survival of more than 60% in the context of an otherwise deadly complication and we observed that the timing of injection and the degree of cytopenia are strongly associated with outcomes. This study shows the feasibility of the procedure informing on its epidemiology, outcomes and prognostic factors, setting the stage for future guidelines.


Subject(s)
Bone Marrow Transplantation , Hematopoietic Stem Cell Transplantation , Humans , Retrospective Studies , Societies, Medical , Hematopoietic Stem Cell Transplantation/adverse effects , Cell- and Tissue-Based Therapy
12.
Front Immunol ; 14: 1106464, 2023.
Article in English | MEDLINE | ID: mdl-36817464

ABSTRACT

Introduction: Poor graft function (PGF) is a rare but serious complication of allogeneic hematopoietic cell transplantation (alloHCT). Due to their hematopoietic supporting properties and immune regulatory effects, multipotent mesenchymal stromal cells (MSC) could be considered a good candidate to help to restore bone marrow (BM) niches homeostasis and facilitate hematopoiesis after alloHCT. Methods: We prospectively assessed the efficacy and safety of ex-vivo expanded BM-derived MSC from third-party donor in a series of 30 patients with prolonged severe cytopenia and PGF after alloHCT. This multicenter trial was registered at www.clinicaltrials.gov (#NTC00603330). Results: Within 90 days post-MSC infusion, 53% (95% CI, 35 - 71%) of patients improved at least one cytopenia (overall response, OR) and 37% (95% CI, 19 - 54%) achieved a complete hematological response (CR: absolute neutrophil count, ANC >0.5 x 109/L, Hb > 80g/L and platelet count > 20 x 109/L with transfusion independence). Corresponding response rates increased to 67% (95% CI, 50 - 84%) OR and 53% (95% CI, 35 - 71%) CR within 180 days after MSC infusion. A significant decrease in red blood cells and platelets transfusion requirement was observed after MSC (median of 30-days transfusion requirement of 0.5 and 0 from d90-120 post-MSC versus 5 and 6.5 before MSC, respectively, p ≤0.001). An increase in ANC was also noted by day +90 and +180, with 3/5 patients with severe neutropenia having recovered an ANC > 1 x 109/L within the 90-120 days after MSC infusion. Overall survival at 1 year post-MSC was 70% (95% CI, 55.4 - 88.5), with all but one of the patients who achieved CR being alive. A single infusion of third-party MSC appeared to be safe, with the exception of one deep vein thrombotic event possibly related to the intervention. Discussion: In conclusion, a single i.v. infusion of BM-derived MSC from third party donor seemed to improve hematological function after alloHCT, although spontaneous amelioration cannot be excluded. Comparative studies are warranted to confirm these encouraging results.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Humans , Mesenchymal Stem Cell Transplantation/methods , Transplantation, Homologous/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects
13.
Transplant Cell Ther ; 29(1): 46.e1-46.e6, 2023 01.
Article in English | MEDLINE | ID: mdl-36210027

ABSTRACT

Poor graft function (PGF) is a life-threatening complication after allogeneic stem cell transplantation (alloSCT). Historically, outcomes of patients with PGF have been very poor, and there are no standardized approaches to treatment. Furthermore, few outcomes after CD34-selected stem cell boost (CD34+SCB) for PGF in pediatric alloSCT recipients have been reported. Here we report on a single center experience with CD34+SCB for PGF after alloSCT in patients treated on the Pediatric Transplant and Cellular Therapy Service at MSK Kids, Memorial Sloan Kettering Cancer Center. A retrospective analysis of patients transplanted for malignant and nonmalignant disorders who received a CD34+SCB between 2008 to 2020 for treatment of PGF defined as the need for granulocyte colony-stimulating factor (G-CSF) and/or packed red blood cell or platelet transfusion support with bone marrow donor chimerism ≥85%. Peripheral blood stem cells from the original donor were the source for CD34+SCB. Durable complete recovery (durable CR) was defined as recovery of peripheral blood counts without recurrent need for G-CSF or transfusion support. The main outcomes of interest were recovery of hematopoiesis and overall survival. Development of graft versus host disease (GVHD) was an additional outcome of interest. Fourteen patients with PGF received a boost. Six patients had no known infection, while 8 patients had PGF associated with an infection. The probability of CR at 60 days was 79% (95% confidence interval [CI], 57%-100%). The overall survival at both 2 and 5 years was 78% (95% CI, 56%-100%). One patient developed GVHD, which was fatal. No other CD34+SCB-related toxicities were observed. While including patients with PGF as recently defined by the American Society for Transplantation and Cellular Therapy, as well as PGF in patients with concomitant infections, we demonstrate that CD34+SCB is safe and can provide for durable trilineage hematopoietic recovery and long-term survival in pediatric patients after alloSCT.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Peripheral Blood Stem Cells , Humans , Child , Retrospective Studies , Transplantation, Homologous/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Antigens, CD34/analysis , Graft vs Host Disease/etiology , Granulocyte Colony-Stimulating Factor/therapeutic use
14.
Leuk Res ; 118: 106870, 2022 07.
Article in English | MEDLINE | ID: mdl-35665626

ABSTRACT

Poor graft function (PGF) and secondary failure of platelet recovery (SFPR) are significant causes of transplant related morbidity and mortality. Although thrombopoietin receptor agonists (TPO-RA), particularly Eltrombopag (EPAG), have been reported to be efficacious in the treatment of prolonged thrombocytopenia, potential long term adverse effects remain to be elucidated. This retrospective study was performed to determine the efficacy and toxicity profile of TPO-RAs in allogeneic hematopoietic stem cell transplant (alloHCT) recipients. Medical records of 27 patients [median age: 55(21-73) years; male/female: 15/12] who received posttransplant EPAG for SFPR or PGF were analysed. Eltrombopag was started on day 110(33-670) after transplant. Median initial dose was 25(25-50) mg/day which was properly escalated to a maximum dose of 75(50-100) mg/day. Duration of the treatment was median 120(31-377) days. Overall response rate (ORR) was 59.3% in the study population. Time-to-treatment response was 42(3-170) days. Mild-to-moderate bone marrow fibrosis was detected in the posttreatment biopsies of 12/22 patients (54.5%), 9 of whom did not represent any grade of myelofibrosis in their inital biopsies. The grade of posttreatment fibrosis was significantly increased when time-to-treatment response was longer (p = 0.008). Long term use of TPO-RAs may be considered as a potential cause of myelofibrosis in alloHCT recipients.


Subject(s)
Hematopoietic Stem Cell Transplantation , Primary Myelofibrosis , Thrombocytopenia , Female , Humans , Male , Middle Aged , Benzoates/adverse effects , Fibrosis , Hematopoietic Stem Cell Transplantation/adverse effects , Hydrazines , Primary Myelofibrosis/drug therapy , Primary Myelofibrosis/etiology , Pyrazoles , Retrospective Studies , Thrombocytopenia/chemically induced , Thrombocytopenia/drug therapy
15.
Front Pharmacol ; 13: 906036, 2022.
Article in English | MEDLINE | ID: mdl-35677428

ABSTRACT

Since its introduction in clinical practice, eltrombopag (ELT) has demonstrated efficacy in heterogeneous clinical contexts, encompassing both benign and malignant diseases, thus leading researchers to make a more in-depth study of its mechanism of action. As a result, a growing body of evidence demonstrates that ELT displays many effects ranging from native thrombopoietin agonism to immunomodulation, anti-inflammatory, and metabolic properties. These features collectively explain ELT effectiveness in a broad spectrum of indications; moreover, they suggest that ELT could be effective in different, challenging clinical scenarios. We reviewed the extended ELT mechanism of action in various diseases, with the aim of further exploring its full potential and hypothesize new, fascinating indications.

16.
Front Immunol ; 13: 911174, 2022.
Article in English | MEDLINE | ID: mdl-35720412

ABSTRACT

Poor graft function (PGF) is a life-threatening complication that occurs after transplantation and has a poor prognosis. With the rapid development of haploidentical hematopoietic stem cell transplantation, the pathogenesis of PGF has become an important issue. Studies of the pathogenesis of PGF have resulted in some success in CD34+-selected stem cell boosting. Mesenchymal stem cells, N-acetyl-l-cysteine, and eltrombopag have also been investigated as therapeutic strategies for PGF. However, predicting and preventing PGF remains challenging. Here, we propose that the seed, soil, and insect theories of aplastic anemia also apply to PGF; CD34+ cells are compared to seeds; the bone marrow microenvironment to soil; and virus infection, iron overload, and donor-specific anti-human leukocyte antigen antibodies to insects. From this perspective, we summarize the available information on the common risk factors of PGF, focusing on its potential mechanism. In addition, the safety and efficacy of new strategies for treating PGF are discussed to provide a foundation for preventing and treating this complex clinical problem.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Soil , Transplantation, Homologous/adverse effects
17.
Front Immunol ; 13: 896034, 2022.
Article in English | MEDLINE | ID: mdl-35615363

ABSTRACT

Secondary poor graft function (sPGF) increases the risk of life-threatening complications after hematopoietic stem cell transplantation (HSCT). The incidence, clinical outcomes, and risk factors of sPGF have not been elucidated in haploidentical (haplo-) HSCT for acquired aplastic anemia (AA) patients. We retrospectively reviewed 423 consecutive AA patients who underwent haplo-HSCT between January 2006 and December 2020 and report a 3-year cumulative incidence of 4.62% (95% confidence interval [CI]: 3.92%-10.23%) of sPGF. While no primary PGF occurred. The median time to sPGF was 121 days (range 30-626 days) after transplantation. To clarify the risk factors for sPGF, 17 sPGF cases and 382 without PGF were further analyzed. Compared to patients without PGF, the 2-year overall survival was significantly poorer for sPGF patients (67.7% vs 90.8%, p =.002). Twelve sPGF patients were alive until the last follow-up, and 7 achieved transfusion independency. The multivariable analyses revealed that later neutrophil engraftment (OR 2.819, p=.049) and a history of refractory cytomegalovirus viremia (OR=7.038, p=.002) post-transplantation were associated with sPGF. There was weak evidence that a history of grade 3-4 acute graft-versus-host disease increased the risk of sPGF (p=.063). We advocated better post-transplantation strategies to balance the risk of immunosuppression and viral reactivation for haplo-HSCT in AA patients.


Subject(s)
Anemia, Aplastic , Hematopoietic Stem Cell Transplantation , Humans , Anemia, Aplastic/epidemiology , Anemia, Aplastic/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Incidence , Retrospective Studies , Risk Factors
18.
Rinsho Ketsueki ; 63(3): 177-181, 2022.
Article in Japanese | MEDLINE | ID: mdl-35387929

ABSTRACT

Herein we report a case of successful treatment of secondary graft failure due to poor graft function (PGF) using eltrombopag. A 25-year-old woman with aplastic anemia (stage 3) underwent allogeneic bone marrow transplantation (BMT) from her HLA-matched brother. Neutrophil engraftment was achieved on day 17, but she remained dependent on platelet transfusion. Chimerism analysis showed complete donor type, but she also became dependent on red blood cell transfusion later. Eltrombopag was administered on day 253 after BMT, after which she exhibited hematopoietic recovery, resulting in the withdrawal of transfusion dependency. Blood counts continued to be stable after eltrombopag was discontinued. The use of eltrombopag enabled outpatient treatment and induced hematopoietic recovery without significant side effects. Eltrombopag may be an effective and safe option for PGF after BMT.


Subject(s)
Anemia, Aplastic , Hematopoietic Stem Cell Transplantation , Adult , Female , Humans , Male , Anemia, Aplastic/etiology , Benzoates , Hematopoietic Stem Cell Transplantation/adverse effects , Hydrazines/therapeutic use , Pyrazoles
19.
Hematology ; 27(1): 293-299, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35192779

ABSTRACT

OBJECTIVES: Graft failure (GF) is an intractable complication of transplantation, which can severely affect the efficacy of the graft; however, the characteristics, incidence, and risk factors of primary GF have not been well described. This study aimed to analyze the risk factors and outcomes of primary GF to swiftly identify high-risk patients for GF. METHODS: We performed a case-control study with a case-control ratio of 1:4 with 869 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2015 and December 2019 at our center. RESULTS: Nineteen (2.19%) patients experienced primary poor graft function (PGF), while eleven (1.27%) patients developed primary graft rejection (GR). Univariate and multivariate logistic analyses identified two independent risk factors for primary PGF: splenomegaly [P = 0.030; odds ratio (OR), 3.486; 95% confidence interval (CI), 1.139 to 13.109], and donor type [non-matched sibling donor (non-MSD)] (P = 0.018; OR, 4.475; 95% CI, 1.289 to 15.537). However, only donor type (non-MSD) was statistically significant (P = 0.020; OR, 19.432; 95% CI, 1.595 to 236.691) for primary GR. The overall survival was significantly lower in the primary PGF (P = 0.001) and GR group (P = 0.000), respectively, compared to the control group. CONCLUSION: GF can significantly affect the overall survival of patients who underwent allo-HSCT, despite its considerably low incidence. A human leukocyte antigen-matched sibling donor should be the first choice for patients undergoing allo-HSCT for the prevention of GF. Moreover, splenomegaly is an independent risk factor for PGF, and caution must be exercised while treating such patients.


Subject(s)
Graft Rejection/physiopathology , Hematopoietic Stem Cell Transplantation/adverse effects , Transplantation Conditioning/adverse effects , Transplantation, Homologous/adverse effects , Adolescent , Adult , Case-Control Studies , Female , Hematopoietic Stem Cell Transplantation/methods , Humans , Male , Middle Aged , Risk Factors , Transplantation Conditioning/methods , Transplantation, Homologous/methods , Treatment Outcome , Young Adult
20.
J Korean Med Sci ; 37(6): e48, 2022 Feb 14.
Article in English | MEDLINE | ID: mdl-35166084

ABSTRACT

Poor graft function (PGF) is a serious, potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation. Eltrombopag has shown multilineage responses in patients with refractory severe aplastic anemia, supporting the idea that it may improve cytopenia in patients with PGF. This retrospective, single center analysis included 8 Korean patients receiving eltrombopag for PGF. Median interval between transplant and eltrombopag treatment was 73 days, and the median duration treatment was 3.5 weeks. With median maximum daily dose of 50 mg, the time to best response was 93 days. Median hemoglobin increased from 8.2 g/dL to 10.9 g/dL, platelet from 18.5 × 109/L to 54 × 109/L, and absolute neutrophil count from 1.25 × 109/L to 3.32 × 109/L. In conclusion, eltrombopag is a good option for PGF in Korean patients, even at a lower dose compared to western patients.


Subject(s)
Benzoates/administration & dosage , Hematopoietic Stem Cell Transplantation/adverse effects , Hydrazines/administration & dosage , Primary Graft Dysfunction/drug therapy , Primary Graft Dysfunction/physiopathology , Pyrazoles/administration & dosage , Adolescent , Adult , Aged , Anemia, Aplastic/drug therapy , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
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