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2.
Cell Transplant ; 32: 9636897231194497, 2023.
Article in English | MEDLINE | ID: mdl-37646153

ABSTRACT

Haploidentical-related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) and cord blood transplantation (CBT) are valid alternatives for patients with hematological malignancies when HLA-matched donor transplantation (MDT) is unavailable. However, the effects of graft-versus-host disease (GVHD) on outcomes after these transplants have not been fully elucidated. Therefore, we evaluated the effects of acute and chronic GVHD on transplant outcomes after PTCy-haplo transplants and compared them with CBT and MDT. We included a total of 914 adult patients with hematological malignancies in the Kyoto Stem Cell Transplantation Group registry who received PTCy-haplo (N = 120), CBT (N = 402), and MDT (N = 392), and achieved neutrophil engraftment. A multivariate analysis revealed that grade I-II acute GVHD improved of overall survival (OS) after PTCy-haplo [hazard ratio (HR) = 0.39, P = 0.018] and CBT (HR = 0.48, P < 0.001), but not after MDT (HR = 0.80, P = 0.267) compared with patients without acute GVHD. Grade I-II acute GVHD had a trend toward reducing the risk of nonrelapse mortality (NRM) after PTCy-haplo (HR = 0.13, P = 0.060) and this positive effect was significant after CBT (HR = 0.39, P = 0.003). A negative impact of grade III-IV acute GVHD on NRM was observed after CBT and MDT, but not after PTCy-haplo. Limited chronic GVHD had a positive impact on OS after CBT and MDT, but not after PTCy-haplo. In conclusion, mild acute GVHD improved outcomes after PTCy-haplo and CBT, and limited chronic GVHD improved outcomes after CBT and MDT. These data indicated that the effects of GVHD on transplant outcomes depended on transplant platforms.


Subject(s)
Bronchiolitis Obliterans Syndrome , Cord Blood Stem Cell Transplantation , Graft vs Host Disease , Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Adult , Humans , Cyclophosphamide/therapeutic use , Cyclophosphamide/pharmacology , Graft vs Host Disease/drug therapy , Hematologic Neoplasms/therapy , Transplantation Conditioning , Retrospective Studies
3.
Ann Hematol ; 102(10): 2909-2922, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37052663

ABSTRACT

Although exposure-directed busulfan (BU) dosing can improve allogeneic hematopoietic stem cell transplantation outcomes, there is still large variability in BU exposure with test dose alone due to changes in BU clearance caused by drug interactions. We conducted a single-arm phase II trial using the combined test dose and therapeutic drug monitoring strategy (PK-guided group) and compared the outcomes with an external historical cohort receiving a fixed-dose (fixed-dose group). The first eight and second eight doses were adjusted based on the area under the blood concentration-time curve (AUC) of the test and first doses, respectively, targeting a total AUC of 82.1 mg·h/L. All patients received either BU and cyclophosphamide conditioning (BU/CY) or fludarabine (FLU)-containing conditioning. The BU clearance at the first dose decreased more in patients receiving FLU than in those receiving BU/CY; however, BU clearance also declined over time in patients who received BU/CY. The simulated total AUC (sAUC) with test dose only was significantly higher in patients who received FLU than in those who received BU/CY, but sAUC with the combined strategy was comparable. The 100-day progression-free survival was 85.5% (95% confidence interval [CI]: 71.9-92.8%), and was not inferior to that in the fixed-dose group. For the FLU-containing regimens, the PK-guided group showed decreased relapse (0.0% vs. 26.9%, p = 0.03), and favorable overall survival (75.1% vs. 57.0%, p = 0.07) at 1 year. The combined strategy effectively controlled the BU exposure close to the target levels, potentially improving efficacy, especially in patients receiving the FLU-containing regimen. Clinical evaluation of efficacy of dose-modified intravenous busulfan in allogeneic hematopoietic stem cell transplantation for hematological malignancy (#UMIN000014077, June 15th, 2014).


Subject(s)
Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Humans , Busulfan , Cyclophosphamide , Drug Monitoring , Hematologic Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Transplantation Conditioning , Vidarabine
4.
Transplant Cell Ther ; 29(6): 347.e1-347.e11, 2023 06.
Article in English | MEDLINE | ID: mdl-36889508

ABSTRACT

Cord blood transplantation (CBT) is an attractive therapeutic option for patients with hematologic malignancies. CBT tolerates HLA mismatches between donors and recipients, but the HLA mismatches that generate graft-versus-tumor (GVT) effects remain unknown. Given that HLA molecules contain epitopes comprising polymorphic amino acids that determine their immunogenicity, we investigated associations between epitope-level HLA mismatches and relapse following single-unit CBT. A total of 492 patients with hematologic malignancies who underwent single-unit, T cell-replete CBT were included in this multicenter retrospective study. HLA epitope mismatches (EMs) were quantified using HLA matchmaker software from donor and recipient HLA-A, -B, -C, and -DRB1 allele data. Patients were dichotomized by median EM value and divided into 2 groups: patients who underwent transplantation in complete/partial remission (standard stage: 62.4%) and others (advanced stage: 37.6%). The median number of EMs in the graft-versus-host direction (GVH-EM) was 3 (range, 0 to 16) at HLA class I and 1 (range, 0 to 7) at HLA-DRB1. Higher HLA class I GVH-EM was associated with increased nonrelapse mortality (NRM) in the advanced stage group (adjusted hazard ratio [HR], 2.12; P = .021), with no significant advantage for relapse in either stage. In contrast, higher HLA-DRB1 GVH-EM was associated with better disease-free survival in the standard stage group (adjusted HR, .63; P = .020), which was attributed to lower relapse risk (adjusted HR, .46; P = .014). These associations also were observed even within HLA-DRB1 allele-mismatched transplantations in the standard stage group, indicating that EM might have an impact on relapse risk independent of allele mismatch. High HLA-DRB1 GVH-EM did not increase NRM in either stage. High HLA-DRB1 GVH-EM may lead to potent GVT effects and a favorable prognosis following CBT, especially in patients who underwent transplantation at the standard stage. This approach may facilitate appropriate unit selection and improve the overall prognosis of patients with hematologic malignancies who undergo CBT.


Subject(s)
Cord Blood Stem Cell Transplantation , Graft vs Host Disease , Hematologic Neoplasms , Humans , HLA-DRB1 Chains/genetics , Epitopes/genetics , Retrospective Studies , Histocompatibility Testing , Neoplasm Recurrence, Local/genetics , Hematologic Neoplasms/genetics , Hematologic Neoplasms/therapy
5.
Int J Hematol ; 117(3): 366-377, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36427162

ABSTRACT

Caplacizumab is an anti-von Willebrand factor humanized single-variable-domain immunoglobulin fragment whose efficacy and safety in immune-mediated thrombotic thrombocytopenia purpura (iTTP) have been demonstrated in international studies. This prospective, open-label phase 2/3 study evaluated caplacizumab 10 mg administered daily during plasma exchange and for 30 days afterward, in combination with immunosuppressive treatment, in Japanese adults with a clinical diagnosis of iTTP (new or recurrent). The primary endpoint was prevention of iTTP recurrence; key secondary endpoints included time to platelet count response, time to organ damage normalization, and safety. Among 21 treated patients, 1 of 15 (6.7%) evaluable patients developed iTTP recurrence. Median time to normalization was 2.79 days for platelet count and 2.65 days for organ damage markers (n = 15). Treatment-emergent adverse events (TEAEs) were mostly mild to moderate in severity; the most frequently reported caplacizumab-related TEAEs were increased alanine aminotransferase, epistaxis, and gastrointestinal hemorrhage (all in 9.5% of patients). At least one bleeding event was reported in 7 of 21 patients (33%). Caplacizumab was effective in Japanese patients with iTTP, with a low rate of iTTP recurrence, rapid normalization of platelet counts and organ damage markers, and no unexpected TEAEs. Trial registration: ClinicalTrials.gov identifier, NCT04074187.


Subject(s)
Purpura, Thrombotic Thrombocytopenic , Single-Domain Antibodies , Adult , Humans , East Asian People , Prospective Studies , ADAMTS13 Protein , Single-Domain Antibodies/therapeutic use , Plasma Exchange , Gastrointestinal Hemorrhage
6.
Transplant Cell Ther ; 28(11): 777.e1-777.e11, 2022 11.
Article in English | MEDLINE | ID: mdl-35964936

ABSTRACT

Relapse is the most common cause of treatment failure after allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). Second or subsequent allogeneic HCT using unrelated cord blood has been performed for adult patients with AML who have relapsed after a previous allogeneic HCT. Although outcomes after unrelated cord blood transplantation (CBT) as the first allogeneic HCT have significantly improved in recent years, it is unclear whether survival and engraftment improve after CBT as the second or subsequent allogeneic HCT for adult AML patients relapsing after a previous allogeneic HCT. The objective of this retrospective study was to evaluate trends of survival and other transplantation outcomes after single-unit unrelated CBT as a second or subsequent allogeneic HCT in adult patients with relapsed AML after a previous allogeneic HCT over the past 19 years in Japan. We retrospectively assessed survival trends and other outcomes of single-unit unrelated CBT as a second or subsequent allogeneic HCT in adult patients with relapsed AML after a previous allogeneic HCT according to the time period of CBT (2001-2007, 2008-2013, or 2014-2019) using a nationwide Japanese database. The median age was 45 years among 1109 CBTs, and 844 (78.6%) patients were not in complete remission at the time of CBT. Over the 3 time periods, there was a progressive increase in higher cryopreserved cord blood total nucleated cell dose and myeloablative conditioning regimens. The 2-year overall survival was 14.0% in 2001-2007, 19.9% in 2008-2013, and 24.4% in 2014-2019 (P <.001 by log-rank trend test). The 2-year relapse-related mortality was 54.0% in 2001-2007, 44.4% in 2008-2013, and 39.1% in 2014-2019 (P < 0.001 by Gray's test), but nonrelapse mortality was not significantly different across the time periods (P = 0.557 by Gray's test). The 42-day neutrophil engraftment also significantly improved (62.9% in 2001-2007, 69.7% in 2008-2013, and 79.9% in 2014-2019; P < 0.001 by Gray's test). Our data demonstrate significant improvements in overall and relapse-related mortality, as well as neutrophil engraftment, after single-unit unrelated CBT as a second or subsequent allogeneic HCT for adult patients with AML relapsed after previous allogeneic HCT over the past 19 years.


Subject(s)
Cord Blood Stem Cell Transplantation , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Adult , Humans , Middle Aged , Retrospective Studies , Japan/epidemiology , Transplantation, Homologous , Leukemia, Myeloid, Acute/therapy , Recurrence
7.
Mod Rheumatol Case Rep ; 6(2): 273-277, 2022 06 24.
Article in English | MEDLINE | ID: mdl-35365826

ABSTRACT

We had two cases of trisomy 8-positive myelodysplastic syndrome (MDS) with incomplete Behçet's disease (BD) in which the remissions of both diseases were maintained by allogeneic stem cell transplantation (allo-SCT). Among MDS with BD patients, sometimes it is difficult to control the symptoms of BD with standard therapies such as corticosteroids and tumor necrosis factor (TNF) inhibitors. Although there should be careful consideration regarding indications for transplantation, our two cases, in which refractory BD was completely controlled by allo-SCT, suggest that allo-SCT can be one of the treatment options for higher-risk MDS with BD patients.


Subject(s)
Behcet Syndrome , Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes , Behcet Syndrome/complications , Behcet Syndrome/diagnosis , Behcet Syndrome/therapy , Chromosomes, Human, Pair 8 , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/therapy , Trisomy
8.
Rinsho Ketsueki ; 63(3): 201-205, 2022.
Article in Japanese | MEDLINE | ID: mdl-35387933

ABSTRACT

The patient is a 34-year-old HIV antibody-negative female with normal immunocompetence. The patient was referred to the hospital of the current study due to diarrhea and abdominal pain, which developed in May 2014. On conducting computed tomography (CT), remarkable wall thickening was noted in the terminal ilium over the ascending colon, suggesting a malignant tumor. However, making a definite diagnosis by lower gastrointestinal endoscopic biopsy and left hemicolectomy was not possible. The dense proliferation of plasma cell-like cells and plasmablasts was noted; CD20, CD19, CD79a, CD3, CD4, and Epstein-Barr virus-encoded miRNAs (EBER) were negative and CD138 was positive on immunostaining. Based on the aforementioned data, the patient was diagnosed with plasmablastic lymphoma (PBL). High-dose chemotherapy combined with autologous peripheral blood stem cell transplantation (PBSCT) was performed in the first remission period after the completion of four cycles of hyper CVAD/MTX-AraC alternating therapy. Remission was confirmed by FDG-PET/CT 3 months after autologous PBSCT. No signs of recurrence have been observed in 6 years after the transplantation. Although no standard treatment for PBL has been established, autologous peripheral blood stem cell transplantation combined with high-dose chemotherapy during the first remission period may be a beneficial treatment option.


Subject(s)
Epstein-Barr Virus Infections , HIV Infections , Peripheral Blood Stem Cell Transplantation , Plasmablastic Lymphoma , Adult , Antineoplastic Combined Chemotherapy Protocols , Female , HIV Infections/complications , Herpesvirus 4, Human , Humans , Plasmablastic Lymphoma/diagnosis , Plasmablastic Lymphoma/therapy , Positron Emission Tomography Computed Tomography , Transplantation, Autologous
9.
Bone Marrow Transplant ; 57(5): 781-789, 2022 05.
Article in English | MEDLINE | ID: mdl-35236933

ABSTRACT

Viral infection is one of the lethal adverse events after cord blood transplantation (CBT). Human leukocyte antigen (HLA) and killer immunoglobulin-like receptor (KIR) ligand divergences can increase the risk of viral infection due to conflicting interactions between virus-infected cells and immune cells. However, the relationship between these disparities and the frequency of viral infection after CBT remains to be evaluated. Herein, we have conducted a retrospective multicenter study to assess the effect of HLA and KIR ligand mismatches on viral infections after CBT. The study included 429 patients, among which 126 viral infections occurred before day 100. Viral infection was significantly associated with poorer overall survival (OS; hazard ratio [HR] 1.74, p < 0.01). Patients harboring ≥3 mismatches in the HLA allele and inhibitory KIR ligand mismatches (HLA & KIR mismatches) had a significantly greater prevalence of viral infection (HR 1.66, p = 0.04). Thus, patients with HLA & KIR mismatches had poorer outcomes in terms of non-relapse mortality (HR 1.61, p = 0.05). Our study demonstrates the unfavorable impacts of HLA & KIR mismatches on viral infections and non-relapse mortality after CBT. Evaluating the viral infection risk and performance of an appropriate and early intervention in high-risk patients and optimizing the graft selection algorithm could improve the outcome of CBTs.


Subject(s)
Cord Blood Stem Cell Transplantation , Hematopoietic Stem Cell Transplantation , Virus Diseases , Cord Blood Stem Cell Transplantation/adverse effects , HLA Antigens , Histocompatibility Antigens Class I , Humans , Ligands , Receptors, KIR/genetics , Risk Factors , Virus Diseases/etiology
10.
Hematology ; 27(1): 239-248, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35152852

ABSTRACT

OBJECTIVES: We conducted a phase II trial to prospectively evaluate the efficacy and safety of bortezomib-cyclophosphamide-dexamethasone (VCD) induction, autologous stem cell transplantation (ASCT), VCD consolidation, and bortezomib maintenance in transplant-eligible newly diagnosed multiple myeloma (NDMM) patients in Japan (UMIN000010542). METHODS: From 2013 to 2016, 42 patients with a median age of 58 (range 42-65) years with NDMM were enrolled in 15 centers. The primary endpoint was the complete response (CR) /stringent CR (sCR) rate after transplantation, and overall/progression-free survival rates were also evaluated. RESULTS: Following induction therapy, the overall response rate was obtained in 71% of patients, including a CR/sCR of 10% and a very good partial response (VGPR) of 26%. Twenty-six of the 42 patients completed ASCT following the protocol and CR/sCR and VGPR rate 100 days after ASCT was 26% and 17%, respectively. During consolidation therapy, 3 of the 24 patients achieved deeper responses. Eight of the 18 patients completed 2-year bortezomib maintenance without disease progression and grade 3/4 toxicities. Five patients were VGPR or partial response after ASCT but maintained response with 2-year bortezomib maintenance. Two-year overall and progression-free survival rates were 92.5% (95% confidence interval [CI]: 78.5%-97.5%) and 62.6% (95% CI: 45.8%-75.5%), respectively. Grade 3/4 toxicities (≥ 10%) included neutropenia (19%) and anemia (17%) in induction, and thrombocytopenia (29%) in consolidation. CONCLUSION: VCD induction/consolidation and bortezomib maintenance with ASCT for NDMM resulted in a high CR/sCR rate and provided good overall/progression-free survival in Japan.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Induction Chemotherapy , Multiple Myeloma , Stem Cell Transplantation , Adult , Aged , Autografts , Bortezomib/administration & dosage , Cyclophosphamide/administration & dosage , Dexamethasone/administration & dosage , Disease-Free Survival , Female , Humans , Japan/epidemiology , Male , Middle Aged , Multiple Myeloma/mortality , Multiple Myeloma/therapy , Prospective Studies , Survival Rate
12.
Blood Adv ; 6(8): 2618-2627, 2022 04 26.
Article in English | MEDLINE | ID: mdl-34933327

ABSTRACT

Graft-versus-host disease-free, relapse-free survival (GRFS) is a useful composite end point that measures survival without relapse or significant morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to develop a novel analytical method that appropriately handles right-censored data and competing risks to understand the risk for GRFS and each component of GRFS. This study was a retrospective data-mining study on a cohort of 2207 adult patients who underwent their first allo-HSCT within the Kyoto Stem Cell Transplantation Group, a multi-institutional joint research group of 17 transplantation centers in Japan. The primary end point was GRFS. A stacked ensemble of Cox Proportional Hazard (Cox-PH) regression and 7 machine-learning algorithms was applied to develop a prediction model. The median age for the patients was 48 years. For GRFS, the stacked ensemble model achieved better predictive accuracy evaluated by C-index than other state-of-the-art competing risk models (ensemble model: 0.670; Cox-PH: 0.668; Random Survival Forest: 0.660; Dynamic DeepHit: 0.646). The probability of GRFS after 2 years was 30.54% for the high-risk group and 40.69% for the low-risk group (hazard ratio compared with the low-risk group: 2.127; 95% CI, 1.19-3.80). We developed a novel predictive model for survival analysis that showed superior risk stratification to existing methods using a stacked ensemble of multiple machine-learning algorithms.


Subject(s)
Hematopoietic Stem Cell Transplantation , Adult , Chronic Disease , Disease-Free Survival , Hematopoietic Stem Cell Transplantation/methods , Humans , Machine Learning , Middle Aged , Recurrence , Retrospective Studies , Risk Factors
13.
Transplantation ; 106(6): 1279-1287, 2022 06 01.
Article in English | MEDLINE | ID: mdl-34935764

ABSTRACT

BACKGROUND: Unrelated cord blood (UCB) and haploidentical related donor transplantation using posttransplant cyclophosphamide (PTCy-haplo) have become alternative options to treat patients with hematological malignancies without a HLA-matched donor. METHODS: We conducted a retrospective study using registry data from the Kyoto Stem Cell Transplantation Group for patients with hematological malignancies who received their first allogeneic hematopoietic cell transplantation using a single UCB unit (n = 460) or PTCy-haplo (N = 57) between 2013 and 2019. RESULTS: We found that overall survival in the UCB group was comparable to that in the PTCy-haplo group (hazard ratio, 1.00; 95% confidence interval, 0.66-1.52), although neutrophil and platelet engraftment were significantly delayed. Nonrelapse mortality risk and the incidence of graft-versus-host disease in the UCB group were also comparable to those in the PTCy-haplo group. Although the relapse risk was similar between the UCB group and the PTCy-haplo group regardless of the disease risk, acute myeloid leukemia patients benefit from UCB transplant with a significantly lower relapse rate (hazard ratio, 0.38; 95% confidence interval, 0.18-0.76). CONCLUSIONS: UCB transplant gives outcomes comparable to PTCy-haplo transplant, and both UCB and PTCy-haplo units are suitable as alternative donor sources for patients without an HLA-matched sibling or unrelated donor.


Subject(s)
Cord Blood Stem Cell Transplantation , Graft vs Host Disease , Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Cord Blood Stem Cell Transplantation/adverse effects , Cyclophosphamide/therapeutic use , Graft vs Host Disease/epidemiology , Graft vs Host Disease/etiology , Graft vs Host Disease/prevention & control , Hematologic Neoplasms/therapy , Humans , Recurrence , Retrospective Studies , Transplantation Conditioning , Unrelated Donors
14.
Rinsho Ketsueki ; 62(11): 1604-1608, 2021.
Article in Japanese | MEDLINE | ID: mdl-34866083

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading across the world. We encountered two patients with COVID-19 who underwent treatment for acute leukemia at initial diagnosis. Both the patients received conventional induction therapy without the exacerbation of COVID-19. Although the impact of SARS-CoV-2 on the treatment of leukemia is unclear, our treatment experience suggests that there is no major contraindication to standard chemotherapy for acute leukemia in patients with COVID-19. As COVID-19 continues to be a threat worldwide, further evaluations of large cohorts are needed for future treatment decisions for acute leukemia with COVID-19.


Subject(s)
COVID-19 , Leukemia , Humans , Polymerase Chain Reaction , SARS-CoV-2
16.
Sci Rep ; 10(1): 21418, 2020 12 08.
Article in English | MEDLINE | ID: mdl-33293600

ABSTRACT

Since the introduction of leukemia-type induction therapies for T-cell lymphoblastic lymphoma (T-LBL), improvements in the long-term outcomes of T-LBL have been reported. However, indications for and the appropriate timing of hematopoietic stem cell transplantation (HSCT) have not yet been established. Therefore, we performed a multicenter retrospective cohort study of patients with T-LBL treated using leukemia-type initial therapies to compare the outcomes after HSCT at different disease stages. We enrolled 21 patients with T-LBL from a total of 11 centers, and all patients received hyper-CVAD as a leukemia-type initial regimen. HSCT was performed during the CR1/PR1 (standard disease) stage in 11 patients, while it was completed at a later or non-remission (advanced disease) stage in 10 patients. Following HSCT, the overall survival rate was significantly greater in standard disease than in advanced-disease patients (79.5% vs. 30.0% at 5 years; hazard ratio (HR) 5.97; p = 0.03), with trend to the lower incidence of relapse in the former group (27.3% vs. 60.0% at 5 years; HR 2.29; p = 0.19). A prognostic difference was not detected between cases treated with allogeneic and autologous HSCTs. Our study suggests that frontline HSCT may be a feasible treatment option for T-LBL, even in the era of leukemia-type initial therapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Hematopoietic Stem Cell Transplantation/methods , Induction Chemotherapy/methods , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Dexamethasone/administration & dosage , Dexamethasone/therapeutic use , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Transplantation, Autologous , Transplantation, Homologous , Treatment Outcome , Vincristine/administration & dosage , Vincristine/therapeutic use , Young Adult
17.
Biol Blood Marrow Transplant ; 26(12): 2346-2358, 2020 12.
Article in English | MEDLINE | ID: mdl-32738500

ABSTRACT

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the key strategy to cure patients with mature T and natural killer (NK) cell lymphomas/leukemia, especially those with relapsed/refractory diseases, there is no consensus strategy for donor selection. We retrospectively analyzed the outcomes of allo-HSCT in 111 patients in 15 Japanese institutions as a multi-institutional joint research project. Thirty-nine patients received bone marrow or peripheral blood stem cell transplantation from related donors (rBMT/rPBSCT), 37 received BMT/PBSCT from unrelated donors (uBMT/uPBSCT), and 35 received cord blood transplantation (CBT). Overall survival (OS) and progression-free survival (PFS) at 4 years were 42% and 34%, respectively. The cumulative incidences of relapse and nonrelapse mortality were 43% and 25%. In multivariate analysis, CBT showed comparable OS with rBMT/rPBSCT (rBMT/rPBSCT versus CBT: hazard ratio [HR], 1.63; P = .264) and better OS compared with uBMT/uPBSCT (HR, 2.99; P = .010), with a trend toward a lower relapse rate (rBMT/rPBSCT versus CBT: HR, 2.60; P = .010; uBMT/uPBSCT versus CBT: HR, 2.05; P = .082). This superiority of CBT was more definite in on-disease patients (OS: rBMT/rPBSCT versus CBT: HR, 5.52; P = .021; uBMT/uPBSCT versus CBT: HR, 6.80; P = .007). Better disease control was also strongly associated with better OS and PFS with lower relapse rate. In conclusion, allo-HSCT is beneficial for the survival of patients with mature T and NK cell lymphomas/leukemia if performed in a timely fashion. Since CBT showed favorable survival with a lower relapse risk, it could be a preferred alternative, especially in on-disease patients.


Subject(s)
Cord Blood Stem Cell Transplantation , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Neoplasms , Bone Marrow Transplantation , Humans , Killer Cells, Natural , Retrospective Studies , T-Lymphocytes
18.
Clin Case Rep ; 8(9): 1791-1792, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32837720

ABSTRACT

This is the first report of a case of COVID-19 after allogeneic stem cell transplantation. Our case suggests that COVID-19 may exist without characteristic CT images, especially in immunocompromised hosts, such as patients after transplantation.

19.
Blood Adv ; 4(13): 3169-3179, 2020 07 14.
Article in English | MEDLINE | ID: mdl-32658984

ABSTRACT

Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, so far, no large cohort study determined the risk factors and the most effective therapeutic strategies for TA-TMA. Thus, the present study aimed to clarify these clinical aspects based on a large multicenter cohort. This retrospective cohort study was performed by the Kyoto Stem Cell Transplantation Group (KSCTG). A total of 2425 patients were enrolled from 14 institutions. All patients were aged ≥16 years, presented with hematological diseases, and received allo-HSCT after the year 2000. TA-TMA was observed in 121 patients (5.0%) on day 35 (median) and was clearly correlated with inferior overall survival (OS) (hazard ratio [HR], 4.93). Pre- and post-HSCT statistically significant risk factors identified by multivariate analyses included poorer performance status (HR, 1.69), HLA mismatch (HR, 2.17), acute graft-versus-host disease (aGVHD; grades 3-4) (HR, 4.02), Aspergillus infection (HR, 2.29), and veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS; HR, 4.47). The response rate and OS significantly better with the continuation or careful reduction of calcineurin inhibitors (CNI) than the conventional treatment strategy of switching from CNI to corticosteroids (response rate, 64.7% vs 20.0%). In summary, we identified the risk factors and the most appropriate therapeutic strategies for TA-TMA. The described treatment strategy could improve the outcomes of patients with TA-TMA in the future.


Subject(s)
Hematopoietic Stem Cell Transplantation , Thrombotic Microangiopathies , Aged , Cohort Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Retrospective Studies , Risk Factors , Thrombotic Microangiopathies/etiology , Thrombotic Microangiopathies/therapy
20.
Ann Hematol ; 98(12): 2815-2823, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31713653

ABSTRACT

Allogeneic hematopoietic stem cell transplantation (allo-SCT) has been considered as a potentially curative treatment option for refractory or relapsed diffuse large B cell lymphoma (DLBCL) patients. However, there is little information available, especially for Japanese patients and in cord blood transplantation (CBT). We aimed to determine treatment outcomes of allo-SCT for DLBCL in the Kyoto Stem Cell Transplantation Group, a multi-institutional joint research group. Sixty-eight DLBCL patients who underwent their first allo-SCT between 2003 and 2016 were included. The median time from diagnosis to transplantation was 13.5 months. Thirty-one patients were in CR/PR at transplantation. Twenty-seven patients underwent CBT. The median follow-up for survivors was 44.2 months. Four-year overall survival (OS) and relapse-free survival (RFS) rates were 23% (95% CI, 13-35%) and 20% (95% CI, 11-31%), respectively. Cumulative incidences of non-relapse mortality and relapse were 23% and 57%, respectively. Patients in CR/PR at allo-SCT had better OS (4-year, 46% vs 4%, P < 0.001) and RFS (4-year, 36% vs 7%, P = 0.005). The source of the stem cell did not significantly affect OS (4-year, bone marrow vs cord blood vs peripheral blood, 28.6% vs 27.2% vs 6.5%, P = 0.193). In multivariate analysis, non-remission status at SCT associated with inferior OS and RFS. Duration from diagnosis to transplantation of less than 1 year associated with inferior RFS. Allo-SCT, including CBT, may be a promising therapeutic modality for DLBCL patients who have good disease control at transplantation.


Subject(s)
Cord Blood Stem Cell Transplantation , Lymphoma, Large B-Cell, Diffuse , Adult , Aged , Allografts , Disease-Free Survival , Female , Follow-Up Studies , Humans , Japan/epidemiology , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/therapy , Male , Middle Aged , Retrospective Studies , Survival Rate
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