scholarly journals Syngeneic hematopoietic stem cell transplantation for acute myeloid leukemia: a propensity score-matched analysis

2021 ◽  
Vol 11 (9) ◽  
Author(s):  
Shuhei Kurosawa ◽  
Shohei Mizuno ◽  
Yasuyuki Arai ◽  
Masayoshi Masuko ◽  
Junya Kanda ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Propensity Score ◽  
Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Acute Myeloid

AbstractThe present study evaluated outcomes and prognostic factors in adult patients with acute myeloid leukemia (AML) after syngeneic hematopoietic stem cell transplantation (HSCT). Among patients in first complete remission (CR1), outcomes of syngeneic HSCT (Syn) were compared with those of autologous HSCT (Auto), allogeneic HSCT from human leukocyte antigen (HLA)-matched sibling donor (MSD), or allogeneic HSCT from HLA-matched unrelated donor (MUD). Among 11,866 patients receiving first HSCT, 26 in the Syn group were analyzed. The 5-year overall survival (OS) rate, the cumulative incidence of relapse, and the cumulative incidence of non-relapse mortality (NRM) were 47.8%, 59.6%, and 4.6%, respectively. The OS was significantly better in patients in CR1 (n = 13) than in patients in non-CR1 (P = 0.012). Furthermore, 39 patients in CR1 each were assigned to the Auto, MSD, and MUD groups using propensity score matching. The 5-year OS in the Syn (68.4%) was not significantly different from those in the Auto (55.9%, P = 0.265), MSD (62.4%, P = 0.419), or MUD (63.7%, P = 0.409) groups. A higher relapse in the Syn than in the MSD and MUD groups was offset by lower NRM. In summary, syngeneic HSCT might be an alternative option for AML patients in CR1.

scholarly journals Prolonged Survival of a Refractory Acute Myeloid Leukemia Patient after a Third Hematopoietic Stem Cell Transplantation with Umbilical Cord Blood following a Second Relapse

2014 ◽  
Vol 2014 ◽  
pp. 1-3
Author(s):  
Suk-young Lee ◽  
Naoki Kurita ◽  
Koichiro Maie ◽  
Masanori Seki ◽  
Yasuhisa Yokoyama ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cord Blood ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Acute Myeloid

Although hematopoietic stem cell transplantation (HSCT) has been considered to be the only way for potential cure of relapsed acute myeloid leukemia (AML), there has been no report on a third HSCT in patients with multiple relapsed AML. Here, we report a case of 53-year-old female who received a successful third allogeneic HSCT after relapse of AML following a second allogeneic HSCT. She was treated with a toxicity reduced conditioning regimen and received direct intrabone cord blood transplantation (CBT) using a single unit of 5/6 HLA-matched cord blood as a graft source. Graft-versus-host disease prophylaxis was performed with a single agent of tacrolimus to increase graft-versus-leukemia effect. She is in remission for 8 months since the direct intrabone CBT. This report highlights not only the importance of individually adjusted approach but also the need for further investigation on the role of HSCT as a treatment modality in patients with refractory or multiple relapsed AML.

scholarly journals αβ-T-cell-depleted haploidentical hematopoietic stem cell transplantation in children with chemorefractory acute myeloid leukemia

2019 ◽  
Vol 18 (2) ◽  
pp. 11-21
Author(s):  
L. N. Shelikhova ◽  
M. A. Ilushina ◽  
K. V. Semiglazova ◽  
Zh. B. Shekhovtsova ◽  
D. A. Shasheleva ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Primary refractory and relapsed refractory acute myeloid leukemia remains an unresolved problem in pediatric oncology. Children with AML who fail to achieve complete remission on high-dose cytarabine and antracyclines have no chance for survival without allogeneic hematopoietic stem cell transplantation. We evaluated the outcome of αβ-T-cell-depleted haploidentical transplantation in a cohort of children with chemorefractory acute myeloid leukemia. Thirty-six patients with either primary refractory (n = 14) or relapsed refractory (n = 22) acute myeloid leukemia in active disease status received a transplantation from haploidentical donors. The preparative regimen included cytoreduction with fludarabine and cytarabine and subsequent treatment with treosulfan and either melphalan or thiophosphamide. Serotherapy consisted of antithymocyte globuline in 14 pts and targeted immunomodulation with tocilizumab +/- abatacept in 22 pts. Grafts were PBSCs engineered by TCR-αβ/CD19 depletion. Posttransplant preemptive therapy included modified donor lymphocyte infusions with or without hypomethylating agents. Complete remission was achieved in 30 (83%) рts. The cumulative incidence of acute GVHD grade II–IV was 25%, and the cumulative incidence of chronic GVHD was 18%. Transplant-related mortality was 6%, and relapse incidence was 48%. Event-free survival was 46%, and overall survival was 41% at 2 years. Good early recovery of NK cells was associated with significantly improved survival and decreased relapse incidence. Our data suggest that αβ-T-cell-depleted haploidentical HSCT provides a reasonable chance of cure in a cohort of children with chemorefractory acute myeloid leukemia and creates a solid basis for further improvement. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology.

scholarly journals Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia Transformed from Ph-Negative Myeloproliferative Neoplasm: A Study from the Adult AML Working Group of the Japan Society for Hematopoietic Cell Transplantation (JSHCT)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2547-2547
Author(s):  
Shinsuke Takagi ◽  
Kazuhiro Masuoka ◽  
Naoyuki Uchida ◽  
Mineo Kurokawa ◽  
Hirohisa Nakamae ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Abstract BACKGROUND/METHODS: Long-term survivors with Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs) can eventually develop acute myeloid leukemia (AML, i.e. blast transformation). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be the only curative treatment for such patients. To clarify its outcome, we retrospectively studied the cases with AML transformed from Ph-neg MPNs using the national registry data of JSHCT. The cases transplanted after 2000 were collected. RESULTS: Thirty-nine cases were extracted (male, n=21; female, n=18). Median age was 57 years (range, 22-71). Underlying Ph-neg MPNs included essential thrombocythemia (ET, n=21), primary myelofibrosis (PMF, n=11) and polycythemia vera (PV, n=7). FAB classification was M0 (n=4), M1 (n=4), M2 (n=10), M3 (n=0), M4 (n=1), M5 (n=3), M6 (n=0), M7 (n=1) and unknown (n=16). Median value of WBC at diagnosis of AML was 8300/uL (250-338000). Karyotype at diagnosis of AML was normal (n=6), complex (n=12), others (n=17) and unknown (n=4). Thirty-two cases (82%) were not in remission at the time of allo-HSCT (1st relapse, n=7; primary induction failure, n=18; untreated, n=12). Median duration between diagnosis of AML and allo-HSCT was 134 days (range, 24-369). The donors were related bone marrow or related mobilized peripheral blood stem cell (rBM/rPBSC, n=8), unrelated bone marrow (uBM, n=15) and unrelated umbilical cord blood (uCB, n=16). Myeloablative conditioning regimens (MAC) were used in 15 cases, and the remaining 24 cases were conditioned by reduced-intensity regimens (RIC), according to CIBMTR definition (Giralt S, et al, 2009). Cumulative incidence of neutrophil engraftment was 74.4% at day 60 (patients engrafted, n=29; death before day 60, n=6; relapse before day 60, n=4). At 2 years after transplant, overall survival (OS) was 29.2%. The median duration of follow up of survivors was 1989.5 days (range, 285-3270). In univariate analysis, age (>57 vs. <57, p=0.87), underlying MPNs (PMF vs. ET vs. PV, p=0.16), disease status at allo-HSCT (CR vs. non-CR, p=0.09), conditioning regimen (MAC vs. RIC, p=0.95) and donor selection (rBM/PBSC vs. uBM vs. uCB, p=0.10) had no impact on OS. The only variable that influenced on OS was chromosome at diagnosis of AML (normal vs. others vs. complex, p=0.02). The cumulative incidence of relapse and non-relapse mortality at 3 years was 34.4% and 38.1%, respectively. CONCLUSION: Although the prognosis of AML transformed from Ph-neg MPNs is dismal in general, the study suggested a promising result that there were curable patients with allo-HSCT. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Donor lymphocyte infusions after first allogeneic hematopoietic stem-cell transplantation in adults with acute myeloid leukemia: a single-center landmark analysis

2021 ◽  
Author(s):  
Andrés R. Rettig ◽  
Gabriele Ihorst ◽  
Hartmut Bertz ◽  
Michael Lübbert ◽  
Reinhard Marks ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Risk Marker ◽  
Single Center ◽  
Hematopoietic Stem ◽  
Acute Myeloid ◽  
Donor Lymphocyte Infusions

AbstractAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is potentially curative for acute myeloid leukemia (AML). The inherent graft-versus-leukemia activity (GvL) may be optimized by donor lymphocyte infusions (DLI). Here we present our single-center experience of DLI use patterns and effectiveness, based on 342 consecutive adult patients receiving a first allo-HSCT for AML between 2009 and 2017. The median age at transplantation was 57 years (range 19–79), and the pre-transplant status was active disease in 58% and complete remission (CR) in 42% of cases. In a combined landmark analysis, patients in CR on day +30 and alive on day +100 were included. In this cohort (n=292), 93 patients received cryopreserved aliquots of peripheral blood-derived grafts for DLI (32%) and median survival was 55.7 months (2-year/5-year probability: 62%/49%). Median survival for patients receiving a first dose of DLI “preemptively,” in the absence of relapse and guided by risk marker monitoring (preDLI; n=42), or only after hematological relapse (relDLI; n=51) was 40.9 months (2-year/5-year: 64%/43%) vs 10.4 months (2-year/5-year: 26%/10%), respectively. Survival was inferior when preDLI was initiated at a time of genetic risk marker detection vs mixed chimerism or clinical risk only. Time to first-dose preDLI vs time to first-dose relDLI was similar, suggesting that early warning and intrinsically lower dynamics of AML recurrence may contribute to effectiveness of preDLI-modified GvL activity. Future refinements of the preemptive DLI concept will benefit from collaborative efforts to diagnose measurable residual disease more reliably across the heterogeneous genomic spectrum of AML.

scholarly journals Magnesium levels and outcome after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia

2020 ◽  
Author(s):  
Linus Angenendt ◽  
Isabel Hilgefort ◽  
Jan-Henrik Mikesch ◽  
Bernhard Schlüter ◽  
Wolfgang E. Berdel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Myeloid Leukemia ◽  
Epstein Barr Virus Infection ◽  
Hematopoietic Stem ◽  
Acute Myeloid

AbstractLow intake of magnesium has been associated with the occurrence of lymphomas and decreased magnesium levels suppress the cytotoxic function of T cells and natural killer cells in patients with “X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia” (XMEN) syndrome. These cell types are also important mediators of immune-mediated effects after allogeneic hematopoietic stem cell transplantation. Here, we show that high posttransplant magnesium levels independently associate with a lower incidence of relapse, a higher risk of acute graft-versus-host disease, and a higher non-relapse mortality in 368 patients with acute myeloid leukemia from our center. Magnesium serum levels might impact on donor-cell-mediated immune responses in acute myeloid leukemia.

scholarly journals CD38-directed CAR-T cell therapy: a novel immunotherapy strategy for relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qingya Cui ◽  
Chongsheng Qian ◽  
Nan Xu ◽  
Liqing Kang ◽  
Haiping Dai ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Cell Therapy ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Stem ◽  
Car T ◽  
Acute Myeloid

AbstractAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). However, most patients experience relapse after allo-HSCT, with a poor prognosis, and treatment options are limited. The lack of an ideal targetable antigen is a major obstacle for treating patients with relapsed AML. CD38 is known to be expressed on most AML and myeloma cells, and its lack of expression on hematopoietic stem cells (HSCs) renders it a potential therapeutic target for relapsed AML. To investigate the clinical therapeutic efficacy and safety of CD38-targeted chimeric antigen receptor T (CAR-T-38) cells, we enrolled 6 AML patients who experienced relapse post-allo-HSCT (clinicaltrials.gov: NCT04351022). Prior to CAR-T-38 treatment, the blasts in the bone marrow of these patients exhibited a median of 95% (92–99%) CD38 positivity. Four weeks after the initial infusion of CAR-T-38 cells, four of six (66.7%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi); the median CR or CRi time was 191 (range 117–261) days. The cumulative relapse rate at 6 months was 50%. The median overall survival (OS) and leukemia-free survival (LFS) times were 7.9 and 6.4 months, respectively. One case relapsed 117 days after the first CAR-T-38 cell infusion, with remission achieved after the second CAR-T-38 cell infusion. All six patients experienced clinically manageable side effects. In addition, multiparameter flow cytometry (FCM) revealed that CAR-T-38 cells eliminated CD38 positive blasts without off-target effects on monocytes and lymphocytes. Although this prospective study has a limited number of cases and a relatively short follow-up time, our preliminary data highlight the clinical utility and safety of CAR-T-38 cell therapy in treating relapsed AML post-allo-HSCT.

Sign in / Sign up

Export Citation Format

Share Document