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1.
Br J Haematol ; 201(1): 106-113, 2023 04.
Article in English | MEDLINE | ID: mdl-36281887

ABSTRACT

Allogeneic haematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for some patients with acute myeloid leukaemia (AML) who are refractory to chemotherapy. Cord blood transplantation (CBT) is a reasonable option in such cases because of its rapid availability. Recently, a growing number of human leucocyte antigen (HLA)-haploidentical related donor HSCTs (haplo-HSCTs) have been performed, although its effectiveness remains undetermined. Using the Japanese nationwide transplantation registry data, we identified 2438 patients aged ≥16 years who received CBT or haplo-HSCT as their first transplant for non-remission AML between January 2008 and December 2018. After 2:1 propensity score matching, 918 patients in the CBT group and 459 patients in the haplo-HSCT group were selected. In this matched cohort, no significant difference in overall survival (OS) was observed between the CBT and haplo-HSCT groups (hazard ratio [HR] of haplo-HSCT to CBT 1.02, 95% confidence interval [CI] 0.89-1.16). Similarly, no significant difference in the cumulative incidence of relapse (HR 1.09, 95% CI 0.93-1.28) or non-relapse mortality (HR 0.94, 95% CI 0.76-1.18). Subgroup analysis showed that CBT was significantly associated with preferable OS in patients receiving myeloablative conditioning. Our data showed comparable outcomes between haplo-HSCT and CBT recipients with non-remission AML.


Subject(s)
Cord Blood Stem Cell Transplantation , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Humans , Retrospective Studies , Transplantation, Haploidentical/adverse effects , Cord Blood Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Neoplasm Recurrence, Local/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, Myeloid, Acute/drug therapy , Transplantation Conditioning/adverse effects
2.
Support Care Cancer ; 30(1): 475-485, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34313857

ABSTRACT

PURPOSE: Bloodstream infection (BSI) is a major complication of allogeneic hematopoietic stem-cell transplantation (allo-SCT). There are several causes of BSI; in particular, severe oral mucositis (OM) can induce BSI due to coagulase-negative staphylococci (CoNS). The OM severity may be reduced with intensive oral care. Thus, we evaluated whether the type of oral care affects the BSI incidence eventually. METHOD: We performed retrospective analysis on 206 recipients who underwent allo-SCT from 2006 to 2017 at our institute. Intensive oral care by a dental specialist was performed for 111 recipients (intensive-care group) and self-oral care was performed by 95 recipients (self-care group). Incidence of BSI was assessed by type of the oral care, before neutrophil engraftment (pre-E-BSI) and after neutrophil engraftment (post-E-BSI) period until 180 days after allo-SCT. RESULT: A total of 112 BSI occurred in 90 of the 206 recipients and 120 bacteria were identified, with CoNS being the most prevalent. There was no significant difference in the incidence of pre-E-BSI between the self-care and intensive-care groups (30.8% and 30.6%, respectively; P = 0.508). Meanwhile, the incidence of post-E-BSI was significantly lower in the intensive-care group than in the self-care group (14.3% and 28.6%; P = 0.008). In addition, the intensive-care group had significantly lower incidence of post-E-BSI with CoNS than the self-care group (8.5% and 21.5%, respectively; P = 0.009). CONCLUSION: Intensive oral care through the period of allo-HCT can significantly reduce the post-E-BSI occurrence, especially due to CoNS.


Subject(s)
Bacteremia , Hematopoietic Stem Cell Transplantation , Sepsis , Bacteremia/epidemiology , Bacteremia/etiology , Bacteremia/prevention & control , Coagulase , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Neutrophils , Retrospective Studies , Risk Factors , Transplantation, Homologous
3.
Eur J Haematol ; 105(5): 616-625, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32705716

ABSTRACT

INTRODUCTION: Chromosome analysis is necessary for the risk classification of acute myeloid leukemia (AML). Marker chromosome (MC) is a fragmented chromosome whose origin cannot be identified from other chromosomes and originates from marked genomic instability. Although AML with MC (MC+) has a poor prognosis even after intensive chemotherapy, its influence on the outcome after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear. OBJECTIVE AND METHODS: We retrospectively analyzed 162 AML patients after allo-HSCT. To evaluate the significance of MC, we compared it with other chromosomal abnormalities. RESULT: Marker chromosome was detected in 14 (8.6%, MC+) patients (vs MC-, n = 158). The 2-year overall survival (OS) in MC+ vs MC- was 26.8% vs 62.2% (P = .0098). The 2-year cumulative incidence of relapse (CIR) in MC+ vs MC- was 80.4% vs 35.5% (P = .0004). Among adverse-risk AML (AD-AML, n = 36), AD-AML/MC+ (n = 11) demonstrated a poorer 2-year OS (9.1%, vs AD-AML/MC- n = 25, 58.3%, P = .0031) and higher 2-year CIR (89.6%, vs AD-AML/MC- 44.7%, P = .002). In multivariate analysis, MC (HR 3.08, 95% CI; 1.02-9.29, P = .046) and HCT-CI (HR 3.23, 95% CI; 1.00-10.4, P = .049) were independent risk factors for CIR among AD-AML. CONCLUSION: Our study suggests MC as a new independent factor for chromosome risk classification to further classify AD-AML.


Subject(s)
Chromosome Aberrations , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Genetic Markers , Genomic Instability , Hematopoietic Stem Cell Transplantation/methods , Humans , Incidence , Leukemia, Myeloid, Acute/epidemiology , Leukemia, Myeloid, Acute/therapy , Prognosis , Recurrence , Transplantation, Homologous , Treatment Outcome
4.
Transfusion ; 57(2): 280-288, 2017 02.
Article in English | MEDLINE | ID: mdl-28144952

ABSTRACT

BACKGROUND: The high prevalence of specific immunoglobulin G for hepatitis E virus (HEV) in Japanese people raises the possibility of a high incidence of HEV-viremic blood donors and therefore frequent transfusion-transmitted HEV (TT-HEV). STUDY DESIGN AND METHODS: TT-HEV cases established in Japan through hemovigilance and those published in the literature were collected. Infectivity of HEV-contaminated blood components and disease severity in relation to immunosuppression were investigated. RESULTS: Twenty established TT-HEV cases were recorded over the past 17 years. A lookback study verified that five of 10 patients transfused with known HEV-contaminated blood components acquired HEV infection. The minimal infectious dose of HEV through transfusion was 3.6 × 104 IU. Nine of the 19 TT-HEV cases analyzed had hematologic diseases. Only two cases showed the maximal alanine aminotransferase level of more than 1000 U/L. Two patients with hematologic malignancy and two liver transplant recipients had chronic liver injury of moderate severity. CONCLUSION: The infectivity of HEV-contaminated components was 50%. Immunosuppression likely causes the moderate illness of TT-HEV, but it may lead to the establishment of chronic sequelae. Transfusion recipients, a population that is variably immunosuppressed, are more vulnerable to chronic liver injury as a result of TT-HEV than the general population is as a result of food-borne infection.


Subject(s)
Antibodies, Viral/blood , Blood Donors , Blood Safety , Blood Transfusion , Hepatitis E virus , Hepatitis E/blood , Hepatitis E/transmission , Immunoglobulin G/blood , Immunosuppression Therapy , Adult , Aged , Aged, 80 and over , Female , Hematologic Neoplasms/blood , Hematologic Neoplasms/therapy , Hepatitis E/epidemiology , Humans , Liver Transplantation , Male , Middle Aged
5.
Clin Transplant ; 31(11)2017 Nov.
Article in English | MEDLINE | ID: mdl-28871665

ABSTRACT

Evaluation methods, such as scoring systems for predicting complications in advance, are necessary for determining the adaptation of allogeneic hematopoietic cell transplantation (HCT) and selecting appropriate conditioning regimens. The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), which is based on functions of main organs, is a useful tool for pre-transplant risk assessments and has been widely applied in determining treatment strategies for patients with hematological diseases. However, as allogeneic HCT is performed on patients with diverse backgrounds, another factor, which reinforces the HCT-CI, is required to evaluate pre-transplant risk assessments. The Glasgow Prognostic Score (GPS), which assesses the combined C-reactive protein and albumin, was reported to predict survival of patients with solid-organ malignancies independently of receiving chemo/radiotherapy and stages of cancer. In this study, we applied the GPS for pre-transplant risk assessments for allogeneic HCT. The GPS successfully stratified the patients into three risk groups of overall survival (OS) and non-relapse mortality (NRM). Moreover, the GPS could predict outcomes independently of the HCT-CI for OS and NRM in multivariate analysis. The GPS is considered to be a useful tool and reinforces the HCT-CI for determining adaptation of allogeneic HCT for patients with hematopoietic neoplasms.


Subject(s)
Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/standards , Neoplasm Recurrence, Local/prevention & control , Preoperative Care/standards , Adolescent , Adult , Aged , Comorbidity , Female , Follow-Up Studies , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/etiology , Neoplasm Recurrence, Local/mortality , Prognosis , Retrospective Studies , Risk Assessment , Survival Rate , Transplantation Conditioning , Transplantation, Homologous , Young Adult
6.
Rinsho Ketsueki ; 58(1): 32-36, 2017.
Article in Japanese | MEDLINE | ID: mdl-28190863

ABSTRACT

A 62-year-old man with CHOP refractory adult T-cell leukemia/lymphoma (ATLL) received anti-CC chemokine receptor 4 antibody (mogamulizumab) combined with CHOP and achieved complete remission. At 71 days after the final administration of mogamulizumab, he received umbilical cord blood transplantation (CBT) using reduced intensity conditioning. Umbilical cord blood engraftment was confirmed on day16. Grade II acute graft-versus-host disease (GVHD) was diagnosed on day60 and was controlled by administration of methylprednisolone. There was no evidence of relapse at 9 months after CBT. Ratios of regulatory T cells in CD4 positive T cells were remarkably low during all of these periods. Since mogamulizumab reduces regulatory T cells, the frequency and severity of acute GVHD were reported to be increased in patients administered mogamulizumab before allogenic stem cell transplantation. Further experiences are needed for selecting optimal donor sources, the portability period and GVHD prophylaxis for patients using mogamulizumab before allogeneic stem cell transplantation.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cord Blood Stem Cell Transplantation , Leukemia-Lymphoma, Adult T-Cell/therapy , Humans , Leukemia-Lymphoma, Adult T-Cell/immunology , Male , Middle Aged , Receptors, CCR4/immunology , Remission Induction , Transplantation, Homologous
7.
Rinsho Ketsueki ; 58(12): 2402-2405, 2017.
Article in Japanese | MEDLINE | ID: mdl-29332874

ABSTRACT

A 75-year-old woman suffered a cat bite 10 months after myelodysplastic syndrome (MDS) diagnosis. She visited our hospital because the internal bleeding of the wound did not improve. Although the wound was treated, the bleeding did not stop. She was hospitalized for emergency medical treatment because the bleeding volume exceeded 200 ml. Although her platelet count was normal, the platelet function test showed a decrease in collagen and arachidonic acid aggregation. After platelet transfusion, her bleeding stopped. Patients with MDS may potentially have platelet dysfunction. In the case of bleeding without thrombocytopenia, a platelet function test should be performed and treatment intervention, such as platelet transfusion, should be considered.


Subject(s)
Blood Platelet Disorders/etiology , Hemorrhage/therapy , Myelodysplastic Syndromes/complications , Aged , Blood Transfusion , Female , Hemorrhage/etiology , Humans , Platelet Aggregation , Treatment Outcome
8.
Rinsho Ketsueki ; 58(8): 905-911, 2017.
Article in Japanese | MEDLINE | ID: mdl-28883272

ABSTRACT

We retrospectively analyzed clinical and pathological features, treatments, and prognoses in 28 patients with newly diagnosed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in Niigata University Medical and Dental Hospital. Of them, 16 were males and 12 were females, and their median age was 62.5 (range, 26-88) years. The International Prognostic Index was high-intermediate/high in 68% of patients. Twelve patients were treated with CHOP/THP-COP and nine with third-generation chemotherapy regimens. At a median follow-up period of 30 (range: 1-164) months, the 2-year overall survival and progression-free survival rates were 61% and 44%, respectively. Further investigation of novel agents for treating PTCL-NOS is warranted.


Subject(s)
Lymphoma, T-Cell, Peripheral/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Follow-Up Studies , Humans , Lymphoma, T-Cell, Peripheral/diagnosis , Male , Middle Aged , Prognosis , Retrospective Studies
10.
Biochem Biophys Res Commun ; 450(1): 837-43, 2014 Jul 18.
Article in English | MEDLINE | ID: mdl-24960197

ABSTRACT

Acute myeloid leukaemia (AML) is a heterogeneous neoplastic disorder in which a subset of cells function as leukaemia-initiating cells (LICs). In this study, we prospectively evaluated the leukaemia-initiating capacity of AML cells fractionated according to the expression of a nucleolar GTP binding protein, nucleostemin (NS). To monitor NS expression in living AML cells, we generated a mouse AML model in which green fluorescent protein (GFP) is expressed under the control of a region of the NS promoter (NS-GFP). In AML cells, NS-GFP levels were correlated with endogenous NS mRNA. AML cells with the highest expression of NS-GFP were very immature blast-like cells, efficiently formed leukaemia colonies in vitro, and exhibited the highest leukaemia-initiating capacity in vivo. Gene expression profiling analysis revealed that cell cycle regulators and nucleotide metabolism-related genes were highly enriched in a gene set associated with leukaemia-initiating capacity that we termed the 'leukaemia stem cell gene signature'. This gene signature stratified human AML patients into distinct clusters that reflected prognosis, demonstrating that the mouse leukaemia stem cell gene signature is significantly associated with the malignant properties of human AML. Further analyses of gene regulation in leukaemia stem cells could provide novel insights into diagnostic and therapeutic approaches to AML.


Subject(s)
GTP-Binding Proteins/genetics , Genetic Predisposition to Disease/genetics , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Nuclear Proteins/genetics , Promoter Regions, Genetic/genetics , Animals , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/pathology , Genetic Markers/genetics , Humans , Mice , Mice, Transgenic , Prognosis
11.
Int J Hematol ; 119(4): 399-406, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38427208

ABSTRACT

INTRODUCTION: The peptide-based cancer vaccine targeting Wilms' tumor 1 (WT1) is a promising immunotherapeutic strategy for hematological malignancies. It remains unclear how long and to what extent the WT1-specific CD8 + cytotoxic T cell (CTL) persist after WT1 peptide vaccination. METHODS: The WT1 peptide vaccine was administered with written consent to a patient with CML in the chronic phase who did not respond well to imatinib, and the patient was followed for 12 years after vaccination. Immune monitoring was performed by specific amplification of WT1-specific CTLs using a mixed lymphocyte peptide culture. T-cell receptors (TCRs) of amplified WT1-specific CTLs were analyzed using next-generation sequencing. This study was approved by the Institutional Review Board of our institution. RESULT: WT1-specific CTLs, which were initially detected during WT1 peptide vaccination, persisted at a frequency of less than 5 cells per 1,000,000 CD8 + T cells for more than 10 years. TCR repertoire analysis confirmed the diversity of WT1-specific CTLs 11 years after vaccination. CTLs exhibited WT1 peptide-specific cytotoxicity in vitro. CONCLUSION: The WT1 peptide vaccine induced an immune response that persists for more than 10 years, even after cessation of vaccination in the CML patient.


Subject(s)
Cancer Vaccines , T-Lymphocytes, Cytotoxic , Humans , Cancer Vaccines/therapeutic use , WT1 Proteins , Vaccines, Subunit , Peptides , Receptors, Antigen, T-Cell , Vaccination
12.
Bone Marrow Transplant ; 59(6): 742-750, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38331981

ABSTRACT

Chronic myelomonocytic leukaemia (CMML) is a haematological malignancy with a poor prognosis. Allogeneic haematopoietic stem cell transplantation remains the only curative approach. Without human leucocyte antigen-matched related sibling donors, the optimal alternative donor has yet to be established. Although unrelated bone marrow transplantation (UBMT) has been extensively studied, cord blood transplantation (CBT) for CMML remains largely unexplored. This nationwide retrospective study compared the outcomes of UBMT and single-unit umbilical CBT in patients with CMML. This study included 118 patients who underwent their first allo-HSCT during 2013-2021. Of these, 50 received BMT (UBMT group), while 68 underwent CBT (CBT group). The primary endpoint was the 3-year overall survival (OS). There were comparable 3-year OS rates between the UBMT (51.0%, 95% confidence interval [CI]: 34.1-65.5%) and CBT (46.2%, 95% CI: 33.2-58.1%; P = 0.60) groups. In the inverse probability of treatment weighting analysis, CBT did not show significantly improved outcomes compared with UBMT regarding the 3-year OS rate (hazard ratio 0.97 [95% CI: 0.57-1.66], P = 0.91). Thus, CBT may serve as an alternative to UBMT for patients with CMML. Further research is necessary to optimise transplantation strategies and enhance outcomes in patients with CMML undergoing CBT.


Subject(s)
Cord Blood Stem Cell Transplantation , Leukemia, Myelomonocytic, Chronic , Humans , Cord Blood Stem Cell Transplantation/methods , Leukemia, Myelomonocytic, Chronic/therapy , Leukemia, Myelomonocytic, Chronic/mortality , Male , Middle Aged , Female , Adult , Retrospective Studies , Aged , Survival Rate
13.
Sci Rep ; 13(1): 13098, 2023 08 11.
Article in English | MEDLINE | ID: mdl-37567982

ABSTRACT

Donor T cell activation, proliferation, differentiation, and migration are the major steps involved in graft-versus-host disease (GVHD) development following bone marrow transplantation. Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and causes immune modulation by interacting with cell growth factors and inducing cell adhesion. However, its precise effects on immune function are unclear than those of other proteoglycan families. Thus, we investigated the significance of CS within donor cells in acute GVHD development utilizing CSGalNAc T1-knockout (T1KO) mice. To determine the effects of T1KO, the mice underwent allogenic bone marrow transplantation from major histocompatibility complex-mismatched donors. While transplantation resulted in hepatic GVHD with inflammatory cell infiltration of both CD4+ and CD8+ effector memory T cells, transplantation in T1KO-donors showed milder cell infiltration and improved survival with fewer splenic effector T cells. In vitro T-cell analyses showed that the ratio of effector memory T cells was significantly lower via phorbol myristate acetate/ionomycin stimulation. Moreover, quantitative PCR analyses showed significantly less production of inflammatory cytokines, such as IFN-γ and CCL-2, in splenocytes of T1KO mice. These results suggest that reduction of CS in donor blood cells may suppress the severity of acute GVHD after hematopoietic stem cell transplantation.


Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Mice , Animals , Chondroitin Sulfates , Transplantation, Homologous/adverse effects , Bone Marrow Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Mice, Inbred C57BL
14.
Cell Death Dis ; 14(9): 642, 2023 Sep 29.
Article in English | MEDLINE | ID: mdl-37773170

ABSTRACT

Differentiation therapy has been proposed as a promising therapeutic strategy for acute myeloid leukemia (AML); thus, the development of more versatile methodologies that are applicable to a wide range of AML subtypes is desired. Although the FOXOs transcription factor represents a promising drug target for differentiation therapy, the efficacy of FOXO inhibitors is limited in vivo. Here, we show that pharmacological inhibition of a common cis-regulatory element of forkhead box O (FOXO) family members successfully induced cell differentiation in various AML cell lines. Through gene expression profiling and differentiation marker-based CRISPR/Cas9 screening, we identified TRIB1, a complement of the COP1 ubiquitin ligase complex, as a functional FOXO downstream gene maintaining an undifferentiated status. TRIB1 is direct target of FOXO3 and the FOXO-binding cis-regulatory element in the TRIB1 promoter, referred to as the FOXO-responsive element in the TRIB1 promoter (FRE-T), played a critical role in differentiation blockade. Thus, we designed a DNA-binding pharmacological inhibitor of the FOXO-FRE-T interface using pyrrole-imidazole polyamides (PIPs) that specifically bind to FRE-T (FRE-PIPs). The FRE-PIPs conjugated to chlorambucil (FRE-chb) inhibited transcription of TRIB1, causing differentiation in various AML cell lines. FRE-chb suppressed the formation of colonies derived from AML cell lines but not from normal counterparts. Administration of FRE-chb inhibited tumor progression in vivo without remarkable adverse effects. In conclusion, targeting cis-regulatory elements of the FOXO family is a promising therapeutic strategy that induces AML cell differentiation.

15.
Int J Hematol ; 113(5): 723-734, 2021 May.
Article in English | MEDLINE | ID: mdl-33502734

ABSTRACT

Wilms' tumor 1 (WT1) is a tumor-associated antigen and immunotherapy target in myelodysplastic syndrome (MDS). Further information is needed on the characteristics of WT1-specific CD8 + T cells to develop immunotherapeutic strategies for MDS. To clarify the frequency, distribution, and phenotype of WT1-specific CD8 + T cells, which occur innately in MDS patients, we analyzed paired peripheral blood (PB) and bone marrow (BM) samples from 39 patients with MDS or acute myeloid leukemia with myelodysplasia-related changes. The median frequency of WT1 tetramer-binding CD8 + T cells in the CD8 + T cell population was 0.11% in PB and 0.18% in BM. A further tetramer assay combined with mixed lymphocyte peptide culture (MLPC assay) was used to detect functional WT1-specific CD8 + T cells that could respond to the WT1 peptide. Functional WT1-specific CD8 + T cells were detected in BM in 61% of patients, which was significantly higher than in PB (23%, p = 0.001). The frequency of these cells estimated by the MLPC assay was tenfold higher in BM than in PB. The majority of WT1 tetramer-binding CD8 + T cells in BM had a unique phenotype with co-expression of CD39 and CXCR4. These findings will facilitate the development of novel immunotherapeutic strategies for MDS.


Subject(s)
Bone Marrow/immunology , CD8 Antigens/analysis , Myelodysplastic Syndromes/immunology , T-Lymphocytes, Cytotoxic/immunology , WT1 Proteins/analysis , Adult , Aged , Aged, 80 and over , CD8 Antigens/immunology , Humans , Middle Aged , WT1 Proteins/immunology
16.
Intern Med ; 58(4): 575-580, 2019 Feb 15.
Article in English | MEDLINE | ID: mdl-30210134

ABSTRACT

A 61-year-old woman exhibited right inguinal lymphadenopathy and right lower limb edema approximately 1 month prior to hospitalization. She was diagnosed with high grade B-cell lymphoma, and a lymph node biopsy and fluorescence in situ hybridization indicated MYC, BCL2, and BCL6 rearrangements (triple-hit lymphoma). She had progressive disease that was CD20-negative after two courses of rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high-dose cytarabine (R-CODOX-M/IVAC) therapy. Subsequent etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin (EPOCH) therapy was not effective. However, after two cycles of gemcitabine, dexamethasone, and cisplatin (GDP) therapy, she achieved a complete response and was able to undergo autologous peripheral blood stem cell transplantation. GDP therapy may be effective as salvage therapy for chemotherapy-resistant triple-hit lymphoma.


Subject(s)
Antineoplastic Agents/therapeutic use , Cisplatin/therapeutic use , DNA-Binding Proteins/genetics , Deoxycytidine/analogs & derivatives , Dexamethasone/therapeutic use , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/genetics , Deoxycytidine/therapeutic use , Female , Gene Rearrangement , Humans , Lymphoma, B-Cell/pathology , Middle Aged , Salvage Therapy , Treatment Outcome , Gemcitabine
17.
J Clin Exp Hematop ; 59(1): 22-28, 2019.
Article in English | MEDLINE | ID: mdl-30918141

ABSTRACT

Hypercalcemia due to malignant tumors including malignant lymphomas is relatively common. Among cancer patients with hypercalcemia, humoral hypercalcemia of malignancy is the most common and accounts for about 80% of all cases with hypercalcemia. 1,25-dihydroxyvitamin D3(1,25(OH)2D3)-mediated hypercalcemia is relatively rare. Although malignant lymphoma has been also reported to cause 1,25(OH)2D3-mediated hypercalcemia, it is not known whether there is any association between 1,25(OH)2D3-mediated hypercalcemia and any specific histological type of malignant lymphoma. We herein report a case of an anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK) -negative with 1,25(OH)2D3-mediated hypercalcemia, which has never been previously reported. An 80-year-old Japanese man was admitted to our department due to acute exacerbation of hypercalcemia. He was diagnosed with ALCL, ALK-negative. Serum 1,25(OH)2D3 level was high and seemed to be associated with the lymphoma because the serum calcium and 1,25(OH)2D3 levels improved in response to chemotherapy. Histological findings showed that many CD68 positive macrophages were observed in the microenvironment of tumor cells. Lymphoma cells or tumor microenvironmental cells may produce 1,25(OH)2D3 because several previous reports showed the source of 1,25(OH)2D3 can be either lymphoma or tumor microenvironmental cells. Moreover, because 1,25(OH)2D3-mediated hypercalcemia has been reported regardless of the specific histological type of lymphoma, tumor microenvironmental cells may be involved in this condition. However, we could not identify the source of 1,25(OH)2D3 in this case. The association between 1,25(OH)2D3 production and prognosis in malignant lymphomas is yet unknown; further studies are needed to elucidate the clinical characteristics of malignant lymphoma with 1,25(OH)2D3-mediated hypercalcemia.


Subject(s)
Hypercalcemia/etiology , Lymphoma, Large-Cell, Anaplastic/complications , Vitamin D/analogs & derivatives , Aged, 80 and over , Fluorodeoxyglucose F18 , Humans , Lymphoma, Large-Cell, Anaplastic/diagnosis , Male , Positron Emission Tomography Computed Tomography , Vitamin D/blood
18.
Cancer Med ; 8(11): 5058-5067, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31305031

ABSTRACT

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for high-risk acute leukemia (AL), some patients still relapse. Since patients simultaneously have many prognostic factors, difficulties are associated with the construction of a patient-based prediction algorithm of relapse. The alternating decision tree (ADTree) is a successful classification method that combines decision trees with the predictive accuracy of boosting. It is a component of machine learning (ML) and has the capacity to simultaneously analyze multiple factors. Using ADTree, we attempted to construct a prediction model of leukemia relapse within 1 year of transplantation. With the model of training data (n = 148), prediction accuracy, the AUC of ROC, and the κ-statistic value were 78.4%, 0.746, and 0.508, respectively. The false positive rate (FPR) of the relapse prediction was as low as 0.134. In an evaluation of the model with validation data (n = 69), prediction accuracy, AUC, and FPR of the relapse prediction were similar at 71.0%, 0.667, and 0.216, respectively. These results suggest that the model is generalized and highly accurate. Furthermore, the output of ADTree may visualize the branch point of treatment. For example, the selection of donor types resulted in different relapse predictions. Therefore, clinicians may change treatment options by referring to the model, thereby improving outcomes. The present results indicate that ML, such as ADTree, will contribute to the decision-making process in the diversified allo-HSCT field and be useful for preventing the relapse of leukemia.


Subject(s)
Algorithms , Clinical Decision-Making/methods , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/therapy , Machine Learning , Patient Participation , Adult , Decision Trees , Disease Management , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Humans , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Models, Theoretical , Prognosis , Survival Analysis , Transplantation, Homologous , Treatment Outcome , Young Adult
19.
Blood Adv ; 3(22): 3626-3634, 2019 11 26.
Article in English | MEDLINE | ID: mdl-31751471

ABSTRACT

Acute graft-versus-host disease (aGVHD) is 1 of the critical complications that often occurs following allogeneic hematopoietic stem cell transplantation (HSCT). Thus far, various types of prediction scores have been created using statistical calculations. The primary objective of this study was to establish and validate the machine learning-dependent index for predicting aGVHD. This was a retrospective cohort study that involved analyzing databases of adult HSCT patients in Japan. The alternating decision tree (ADTree) machine learning algorithm was applied to develop models using the training cohort (70%). The ADTree algorithm was confirmed using the hazard model on data from the validation cohort (30%). Data from 26 695 HSCT patients transplanted from allogeneic donors between 1992 and 2016 were included in this study. The cumulative incidence of aGVHD was 42.8%. Of >40 variables considered, 15 were adapted into a model for aGVHD prediction. The model was tested in the validation cohort, and the incidence of aGVHD was clearly stratified according to the categorized ADTree scores; the cumulative incidence of aGVHD was 29.0% for low risk and 58.7% for high risk (hazard ratio, 2.57). Predicting scores for aGVHD also demonstrated the link between the risk of development aGVHD and overall survival after HSCT. The machine learning algorithms produced clinically reasonable and robust risk stratification scores. The relatively high reproducibility and low impacts from the interactions among the variables indicate that the ADTree algorithm, along with the other data-mining approaches, may provide tools for establishing risk score.


Subject(s)
Algorithms , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Machine Learning , Area Under Curve , Female , Hematologic Diseases/complications , Hematologic Diseases/therapy , Humans , Male , Models, Theoretical , Prognosis , Reproducibility of Results , Transplantation, Homologous/adverse effects
20.
Int J Hematol ; 108(3): 282-289, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29744806

ABSTRACT

The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) is a widely used tool for pre-transplant risk assessment. Allogeneic hematopoietic cell transplantation (HCT) is performed on patients with diverse backgrounds, highlighting the need for other predictors to complement the HCT-CI and support bedside decision-making. There is a strong body of evidence supporting the use of pre-transplant serum ferritin (SF) in risk assessments of allogeneic HCT. We additionally found that the Glasgow Prognostic Score (GPS), which assesses inflammatory biomarkers and predicts survival of patients with solid organ malignancies, is a useful predictive marker for overall survival (OS) and non-relapse mortality (NRM) in allogeneic HCT, independent of HCT-CI and SF. In this study, we refined the GPS by adding pre-transplant SF to improve its prognostic ability and enable better stratification; we call this revised index the HCT-specific revised Glasgow Prognostic Score (HCT-GPS). We observed that the HCT-GPS more accurately predicted NRM and early-term OS than the GPS. Moreover, the HCT-GPS provides an independent prognostic factor adjusted for the HCT-CI and disease status, and stratifies patients into four risk groups by OS and NRM. Thus, the HCT-GPS is a useful index for predicting early-term complications after allogeneic HCT in patients with hematopoietic diseases.


Subject(s)
Hematologic Neoplasms/diagnosis , Hematopoietic Stem Cell Transplantation/mortality , Prognosis , Adolescent , Adult , Aged , Comorbidity , Female , Ferritins/blood , Hematologic Neoplasms/mortality , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Male , Middle Aged , Risk Assessment , Survival Analysis , Transplantation, Homologous/adverse effects , Transplantation, Homologous/mortality
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