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1.
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
2.
Bone Marrow Transplant ; 57(5): 810-816, 2022 05.
Article in English | MEDLINE | ID: mdl-35314792

ABSTRACT

Chromosome analysis is a powerful prognostic tool in myeloid malignancies. Recipients who experience relapse after allogeneic hematopoietic cell transplantation (allo-HCT) often show chromosomal changes between diagnosis and relapse. However, the clinical impact of chromosomal changes and the efficacy of post-relapse treatment according to chromosomal changes have not been fully investigated. We retrospectively analyzed 72 recipients who had experienced relapse after allo-HCT for acute myeloid leukemia or myelodysplastic syndrome. We categorized them into two groups: with or without clonal chromosomal changes at relapse after allo-HCT. Post-relapse survival was shorter in the clonal chromosomal change group (median 117 days vs 275 days, P = 0.019). Moreover, acquisition of chromosome 7 abnormality or complex changes tended to be associated with inferior survival in a univariate analysis (median 92 days vs median 173 days, P = 0.043), and this adverse impact was confirmed in a multivariate analysis (hazard ratio 2.07, P = 0.024). The patterns of chromosomal changes from diagnosis to relapse after allo-HCT were heterogenous, and further investigations are required to clarify the effect of individual chromosomal changes.


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Chromosomes , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/therapy , Prognosis , Recurrence , Retrospective Studies
3.
Acta Haematol ; 145(6): 582-591, 2022.
Article in English | MEDLINE | ID: mdl-35016184

ABSTRACT

INTRODUCTION: Chromosomal abnormalities (CAs) have been identified as important factors in determining the biological features and prognostic value of multiple myeloma (MM). MYC gene-related abnormalities (MYC GAs) are one of the CAs, but their unfavorable impact has not been fully investigated in daily clinical practice. METHODS: This study retrospectively analyzed the prognostic impact of MYC GAs on 81 patients through fluorescence in situ hybridization analysis in our institute. RESULTS: MYC GAs were associated with poor overall survival (hazard ratio [HR], 3.08; 95% confidence interval [CI]: 1.23-7.73; p = 0.017), progression-free survival (PFS) (HR, 2.96; 95% CI: 1.58-5.53; p < 0.001), and time to next treatment (TNT) (HR, 2.11; 95% CI: 1.13-3.93; p = 0.018) in the median follow-up of 34.7 months. Furthermore, MYC GAs with an additional chromosome 8 (MYC-Ch8(+)) were associated with shorter PFS (HR, 3.15; 95% CI: 1.38-7.2; p = 0.0064), whereas MYC GAs without an additional chromosome 8 (MYC-Ch8(-)) were associated with shorter PFS (HR, 3.62; 95% CI: 1.51-8.68; p = 0.004) and shorter TNT (HR, 3.72; 95% CI: 1.41-9.81; p = 0.0078). CONCLUSION: These findings could help identify high-risk patients with MM. Further prospective studies are needed to confirm the significance of MYC GAs for the MM prognostic effect.


Subject(s)
Multiple Myeloma , Humans , Multiple Myeloma/diagnosis , Multiple Myeloma/genetics , Multiple Myeloma/drug therapy , Genes, myc , Prognosis , In Situ Hybridization, Fluorescence , Retrospective Studies , Chromosome Aberrations
4.
Rinsho Ketsueki ; 63(12): 1653-1656, 2022.
Article in Japanese | MEDLINE | ID: mdl-36653139

ABSTRACT

A 65-year-old man was diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia with no initial central nervous system (CNS) involvement. Complete remission was achieved after the induction therapy. However, during consolidation therapy, he developed septic shock and pneumocystis pneumonia, leading to interruption in chemotherapy and allogeneic transplantation. Subsequently, he achieved complete molecular remission and ponatinib maintenance therapy was initiated. Two years later, he developed left leg paralysis and was diagnosed with isolated CNS relapse; however, radiation therapy improved CNS lesions and paralysis. Thus, ponatinib maintenance therapy alone is inadequate in preventing CNS relapse in patients who have not completed systemic chemotherapy for CNS relapse prevention.


Subject(s)
Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Male , Humans , Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Chronic Disease , Central Nervous System , Recurrence , Paralysis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
5.
Rinsho Ketsueki ; 62(1): 20-24, 2021.
Article in Japanese | MEDLINE | ID: mdl-33551420

ABSTRACT

Patients with refractory ascites that develops >3 months after allogenic stem cell transplantation typically have a poor prognosis. We present the case of a 61-year-old man who developed refractory massive ascites approximately 3 months after cord blood transplantation (CBT) and showed complete and spontaneous remission from ascites after 18 months. The patient complained of severe bloating and needed weekly paracentesis to manage the fluid levels. Laboratory tests indicated that the ascites was caused by liver fibrosis. After the patient underwent Keisuke-Matsusaki cell-free and concentrated ascites reinfusion therapy (KM-CART), we were able to decrease the frequency of paracentesis treatments. We planned a transjugular liver biopsy, but the patient contracted pneumocystis pneumonia before the procedure could be performed. Although the pneumonia improved, the ascites worsened again. However, weekly paracentesis spontaneously stopped the progression of ascites and eventually resolved it completely, resulting in the patient's survival.


Subject(s)
Ascites , Cord Blood Stem Cell Transplantation , Leukemia, Myeloid, Acute , Ascites/etiology , Ascites/therapy , Humans , Leukemia, Myeloid, Acute/therapy , Liver Cirrhosis/complications , Liver Cirrhosis/therapy , Male , Middle Aged , Paracentesis
6.
Rinsho Ketsueki ; 61(6): 598-604, 2020.
Article in Japanese | MEDLINE | ID: mdl-32624531

ABSTRACT

This retrospective study evaluated the outcomes of patients treated with combination of bendamustine and rituximab (BR) for recurrent indolent B-cell lymphoma from January 2011 to February 2018 in our department. The cohort included 36 males and 27 females, and majority of the patients (59%) were between 51 and 70 years of age. The disease types were follicular lymphoma (FL) and mantle-cell lymphoma in 42 (67%) and 15 (24%) patients, respectively. Median progression-free survival (PFS) was not reached in patients with FL who completed BR therapy. The analysis of patients who received BR therapy revealed that the number of CD4-positive lymphocytes remained around 200/µl even five years after the end of treatment. BR therapy was a useful treatment option for recurrent indolent B-cell lymphoma, especially in patients with FL, and completion of BR therapy appeared to be important for improved PFS. Furthermore, attention should be paid for potential infections for at least five years after BR therapy because cell-mediated immunodeficiency may become apparent after treatment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, B-Cell , Aged , Bendamustine Hydrochloride , Female , Humans , Lymphoma, B-Cell/drug therapy , Male , Middle Aged , Neoplasm Recurrence, Local , Retrospective Studies , Rituximab
7.
Blood ; 134(10): 814-825, 2019 09 05.
Article in English | MEDLINE | ID: mdl-31270105

ABSTRACT

Monocyte-derived fibrocytes recently garnered attention because the novel pathogenesis of myelofibrosis (MF), and suppression of fibrocyte differentiation by serum amyloid P remarkably improved MF. We previously revealed that human fibrocytes highly expressed signaling lymphocytic activation molecule F7 (SLAMF7) compared with macrophages and that SLAMF7high monocytes in the peripheral blood (PB) of MF patients were significantly elevated relative to those in healthy controls (HCs). In this study, we evaluated SLAMF7high monocyte percentage in the PB of HCs, myeloproliferative neoplasm (MPN) patients with MF, and MPN patients without MF by using a cross-sectional approach. We found that MPN patients with MF who harbored JAK2V617F had a significantly elevated SLAMF7high monocyte percentage, which correlated positively with the JAK2V617F allele burden. In addition, the serum concentration of interleukin-1ra (IL-1ra) was significantly correlated with the SLAMF7high monocyte percentage and JAK2V617F allele burden. These findings suggest that both SLAMF7high monocytes and IL-1ra could be useful noninvasive markers of MF onset. Furthermore, the JAK2V617F allele burden of SLAMF7high monocytes was significantly higher than that of SLAMF7low monocytes and could be a potential target of elotuzumab (Elo), an anti-SLAMF7 antibody used for treating multiple myeloma. Elo independently inhibited differentiation of fibrocytes derived not only from HCs but also from MF patients in vitro. Elo also ameliorated MF and splenomegaly induced by romiplostim administration in humanized NOG mice. In conclusion, an increase of SLAMF7high monocytes with higher JAK2V617F allele burden was associated with the onset of MF in MPN patients harboring JAK2V617F, and Elo could be a therapeutic agent for MPN patients with MF who harbor JAK2V617F.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Janus Kinase 2/genetics , Monocytes/pathology , Primary Myelofibrosis/drug therapy , Primary Myelofibrosis/genetics , Adult , Aged , Aged, 80 and over , Amino Acid Substitution , Blood Cell Count , Cell Proliferation , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Molecular Targeted Therapy , Monocytes/metabolism , Mutation, Missense , Phenylalanine/genetics , Primary Myelofibrosis/blood , Primary Myelofibrosis/pathology , Signaling Lymphocytic Activation Molecule Family/metabolism , Valine/genetics
8.
Rinsho Ketsueki ; 60(12): 1647-1651, 2019.
Article in Japanese | MEDLINE | ID: mdl-31902815

ABSTRACT

A 69-year-old woman presented to National Defense Medical College hospital for suspected nephrotic syndrome due to weight gain of 30 kg in 3 weeks and bilateral lower leg edema. However, her urinalysis showed microproteinuria, which excluded nephrotic syndrome. Computed tomography revealed severe systemic edema, pleural effusion, ascites, and enlarged cervical and axillary lymph nodes. Histological examination of axillary lymph node specimen showed a typical architecture of angioimmunoblastic T-cell lymphoma. One course of CHOP chemotherapy regimen was administered which improved the lymph nodes and systemic edema. The patient achieved complete remission after 6 courses of CHOP. Because serum vascular endothelial growth factor (VEGF) level was elevated before the treatment and normalized after the treatment, increased vascular permeability mediated by VEGF was hypothesized to have caused the systemic edema. In addition, VEGF secretion from Epstein-Barr virus (EBV)-infected cells was likely associated with the patient's clinical condition because B lymphocytes stained with CD20 were positive for Epstein-Barr virus-encoded small RNAs (EBERs) and VEGF.


Subject(s)
Immunoblastic Lymphadenopathy , Lymphoma, T-Cell , Aged , Edema , Female , Herpesvirus 4, Human , Humans , Vascular Endothelial Growth Factor A
9.
PLoS One ; 13(11): e0207149, 2018.
Article in English | MEDLINE | ID: mdl-30408105

ABSTRACT

Mucosal-associated invariant T (MAIT) cells help protect against certain infections and are related to some autoimmune diseases. Immune thrombocytopenia (ITP) is a relatively rare hematological autoimmune disease associated with low platelet count. We designed a cross-sectional study wherein we examined peripheral blood samples of patients with ITP for the number of MAIT cells (CD3+TCR-Vα7.2+CD161+IL-18Rα+ lymphocytes) and their CD4/8 subsets (by flow cytometry) and levels of cytokines (by multiplex assays). The study cohort included 18 patients with ITP and 20 healthy controls (HCs). We first compared the number of MAIT cells between HCs and patients with ITP and then performed subgroup analysis in patients with ITP. The number of total MAIT cells in patients with ITP was significantly lower than that in HCs (p < 0.0001), and the CD4-CD8+ subset of MAIT cells showed the same trend. Moreover, patients with ITP refractory to prednisolone exhibited a significantly lower number of total MAIT and CD4-CD8+ MAIT cells than patients sensitive to prednisolone. The number of total MAIT and CD4-CD8+ MAIT cells was not correlated with the response to thrombopoietin receptor agonist treatment or with Helicobacter pylori infection. We found no relation between cytokine levels and response to prednisolone treatment, although the levels of IP-10 and RANTES showed a correlation with the number of total MAIT and CD4-CD8+ MAIT cells. In conclusion, total MAIT and CD4-CD8+ MAIT cells in peripheral blood were decreased in patients with ITP, correlating with their response to prednisolone.


Subject(s)
Mucosal-Associated Invariant T Cells/drug effects , Mucosal-Associated Invariant T Cells/immunology , Prednisolone/therapeutic use , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/immunology , Adult , Aged , Aged, 80 and over , Case-Control Studies , Chemokine CCL5/blood , Chemokine CXCL10/blood , Cohort Studies , Cross-Sectional Studies , Cytokines/blood , Female , Glucocorticoids/therapeutic use , Humans , Lymphocyte Count , Male , Middle Aged , Mucosal-Associated Invariant T Cells/pathology , Purpura, Thrombocytopenic, Idiopathic/blood , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/pathology , Treatment Outcome
10.
Int J Hematol ; 107(4): 495-497, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29032513

ABSTRACT

Sudden blast phase (SBP) is a rare event in which patients with chronic myeloid leukemia (CML) in complete cytogenetic response (CCyR) rapidly progress to the blast phase. Few patients on second-generation tyrosine kinase inhibitors (2nd TKIs) have been reported to develop SBP. Here, we report a 45-year-old man diagnosed with CML in the chronic phase in April 2008 and immediately started on imatinib therapy. He achieved CCyR 12 months after starting imatinib therapy. Imatinib was followed by treatment with the 2nd TKIs nilotinib and dasatinib from January 2011 to yield a better response. He achieved major molecular response (MMR) during dasatinib therapy in February 2012, but did not tolerate dasatinib well; hence, he was switched to nilotinib in July 2012. In December 2015, he presented at our hospital with fever and lumbago. A complete blood count revealed a white blood cell count of 30,500/µL with 60% blasts, leading to diagnosis of SBP. After dasatinib therapy and conventional chemotherapy, he again achieved MMR. This case demonstrates that SBP may occur after achieving MMR on treatment with 2nd TKIs. Continuous careful monitoring is required for the early detection of SBP, even in patients who have achieved MMR.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blast Crisis , Drug Substitution/adverse effects , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Dasatinib/administration & dosage , Disease Progression , Drug Resistance, Neoplasm , Humans , Imatinib Mesylate/administration & dosage , Male , Middle Aged , Protein-Tyrosine Kinases/antagonists & inhibitors , Treatment Outcome
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