Novel lysyl oxidase inhibitors attenuate hallmarks of primary myelofibrosis in mice.
Abstract Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm (MPN) that usually portends a poor prognosis with limited therapeutic options available. Currently, only allogeneic stem cell transplantation is curative in those who are candidates, while administration of the JAK1/2 inhibitor ruxolitinib carries a risk of worsening cytopenia. The limited therapeutic options available highlight the need for the development of novel treatments for PMF. Lysyl oxidase (LOX), an enzyme vital for collagen cross-linking and extracellular matrix stiffening, has been found to be upregulated in PMF. Herein, we e...
Source: International Journal of Hematology - October 21, 2019 Category: Hematology Authors: Leiva O, Ng SK, Matsuura S, Chitalia V, Lucero H, Findlay A, Turner C, Jarolimek W, Ravid K Tags: Int J Hematol Source Type: research

Mutational profiling in myelofibrosis: implications for management.
Abstract Mutational profiling, usually by targeted next-generation sequencing, is increasingly performed on patients with myeloproliferative neoplasm-associated myelofibrosis (MF), whether primary (PMF) or post-polycythemia vera/essential thrombocythemia (post-PV/ET MF). "Driver" mutations in JAK2, MPL and indels in CALR underlie the vast majority of cases of PMF and post-ET MF; the remainder (≈ 10%) lack identifiable driver mutations, but other clonal markers are usually detectable. Nearly all patients with post-PV MF carry activating JAK2 mutations. In both PMF and post-ET MF, type 1/-like...
Source: International Journal of Hematology - October 19, 2019 Category: Hematology Authors: Bose P, Verstovsek S Tags: Int J Hematol Source Type: research

Successful outcome with reduced-intensity condition regimen followed by allogeneic hematopoietic stem cell transplantation for relapsed or refractory anaplastic large-cell lymphoma.
We report a retrospective analysis of 38 patients (age ≤ 30 years) who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT) for relapsed or refractory anaplastic large-cell lymphoma (ALCL). Median follow-up for survivors after undergoing allo-SCT was 72 months (range, 35-96 months). Eight patients received reduced-intensity conditioning (RIC) regimens, including three patients with fludarabine plus melphalan-based regimens and five patients with fludarabine plus busulfan-based regimens. The remaining 30 patients received myeloablative conditioning (MAC) regimens. Median ages in the RIC ...
Source: International Journal of Hematology - October 16, 2019 Category: Hematology Authors: Fukano R, Mori T, Fujita N, Kobayashi R, Mitsui T, Kato K, Suzuki R, Suzumiya J, Fukuda T, Shindo M, Maseki N, Shimoyama T, Okada K, Inoue M, Inagaki J, Hashii Y, Sato A, Tabuchi K Tags: Int J Hematol Source Type: research

Autologous hematopoietic cell transplantation for acute myeloid leukemia in adults: 25  years of experience in Japan.
Autologous hematopoietic cell transplantation for acute myeloid leukemia in adults: 25 years of experience in Japan. Int J Hematol. 2019 Oct 14;: Authors: Yanada M, Takami A, Mizuno S, Mori J, Chou T, Usuki K, Uchiyama H, Amano I, Fujii S, Miyamoto T, Saito T, Kamimura T, Ichinohe T, Fukuda T, Okamoto S, Atsuta Y, Yano S Abstract Autologous hematopoietic cell transplantation (HCT) has not gained universal popularity in the treatment of acute myeloid leukemia (AML), and its status remains unclear. To determine the implementation status and outcomes of autologous HCT for adults with AML in Japan, w...
Source: International Journal of Hematology - October 14, 2019 Category: Hematology Authors: Yanada M, Takami A, Mizuno S, Mori J, Chou T, Usuki K, Uchiyama H, Amano I, Fujii S, Miyamoto T, Saito T, Kamimura T, Ichinohe T, Fukuda T, Okamoto S, Atsuta Y, Yano S Tags: Int J Hematol Source Type: research

Muscle aches and pains: do I have leukemia?
We describe a 65-year-old man who presented with 'aches and pains' localized to the lower extremities, and was diagnosed with acute myeloid leukemia (AML). We hypothesize that this case represents an atypical presentation of AML with an immune-mediated necrotizing-like myopathy as a possible paraneoplastic manifestation of the disease, which improved after initiating chemotherapy. Our patient received a full course of 7 + 3 chemotherapy with cytarabine and daunorubicin. Proximal leg weakness and pain improved markedly following this treatment, establishing a temporal relationship between the possible paraneop...
Source: International Journal of Hematology - October 14, 2019 Category: Hematology Authors: Deschner M, Phua C, Saini L, Xenocostas A, Deotare U Tags: Int J Hematol Source Type: research

Idiopathic anaphylaxis and systemic mastocytosis.
PMID: 31606842 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
Source: International Journal of Hematology - October 12, 2019 Category: Hematology Authors: Francischetti IMB, Maric I Tags: Int J Hematol Source Type: research

Identification of a missense mutation (p.Leu1733Pro) in the A3 domain of von Willebrand factor in a family with type 2M von Willebrand disease.
Abstract The proband's von Willebrand factor (VWF) antigen and VWF collagen-binding capacity were 14% and 10%, respectively; his sister's were 16% and 9%, respectively; and his nephew's were 30% and 15%, respectively. No apparent loss of high-molecular weight VWF multimers was observed in the plasma of these patients. A single-nucleotide substitution of T to C was found at nucleotide position 113042 in their VWF gene, converting Leu1733 to Pro in the A3 domain. These results suggest that p.Leu1733Pro is responsible for type 2M von Willebrand disease in this family. PMID: 31605304 [PubMed - as supplied by publ...
Source: International Journal of Hematology - October 11, 2019 Category: Hematology Authors: Shigekiyo T, Yagi H, Sekimoto E, Shibata H, Ozaki S, Matsumoto M Tags: Int J Hematol Source Type: research

Successful granulocyte apheresis using medium molecular weight hydroxyethyl starch.
In this study, we evaluated the efficiency of granulocyte collection using medium molecular weight HES (130 kDa) in combination with the Spectra Optia apheresis system. Apheresis was performed for 2 consecutive days from seven donors and the mean total neutrophil yield from the first and second apheresis was 5.27 ± 3.10 × 1010 and 2.91 ± 2.92 × 1010, respectively. Infusion of concentrates from the first apheresis resulted in a significant neutrophil count increase and concentrates from the second apheresis were enough for maintenance of ...
Source: International Journal of Hematology - October 10, 2019 Category: Hematology Authors: Nanya M, Yurugi K, Kato I, Hiramatsu H, Kawabata H, Kondo T, Iemura T, Hishida R, Shibutani E, Matsui K, Nakagawa Y, Niwa N, Kasai Y, Roig JM, Arai Y, Miura Y, Takaori-Kondo A, Maekawa T, Hirai H Tags: Int J Hematol Source Type: research

A megakaryocyte in a peripheral blood smear.
PMID: 31587146 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
Source: International Journal of Hematology - October 5, 2019 Category: Hematology Authors: Nakai T, Okamoto Y Tags: Int J Hematol Source Type: research

Intestinal thrombotic microangiopathy: a distinct entity in the spectrum of graft-versus-host disease.
In conclusion, iTMA emerges as a novel distinct entity in patients with GVHD and/or TA-TMA. Distinct histological features may be useful in differential diagnosis of these severe HCT complications. The higher mortality rates of iTMA than TA-TMA highlight the need for further investigation of this condition. PMID: 31586304 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
Source: International Journal of Hematology - October 4, 2019 Category: Hematology Authors: Gavriilaki E, Sakellari I, Karafoulidou I, Pasteli N, Batsis I, Mallouri D, Lazaridou A, Iskas M, Vardi A, Papalexandri A, Tsompanakou A, Papaemmanouil S, Ilias A, Anagnostopoulos A Tags: Int J Hematol Source Type: research

TERT and JAK2 polymorphisms define genetic predisposition to myeloproliferative neoplasms in Japanese patients.
In conclusion, we demonstrated that both TERT rs2736100_C and JAK2 46/1 haplotype are predisposing factors for MPNs in Japanese patients. While TERT rs2736100_C tended to have a more general, non-specific effect on all MPNs, the JAK2 46/1 haplotype was essentially predisposed to the JAK2 V617F-positive MPNs. PMID: 31571131 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
Source: International Journal of Hematology - September 30, 2019 Category: Hematology Authors: Matsuguma M, Yujiri T, Yamamoto K, Kajimura Y, Tokunaga Y, Tanaka M, Tanaka Y, Nakamura Y, Tanizawa Y Tags: Int J Hematol Source Type: research

Phase I study of graft-versus-host disease prophylaxis including bortezomib for allogeneic hematopoietic cell transplantation from unrelated donors with one or two HLA loci mismatches in Japanese patients.
Abstract This phase I study was designed for graft-versus-host disease (GVHD) prophylaxis including bortezomib in allogeneic hematopoietic cell transplantation (allo-HCT) from human leukocyte antigen (HLA)-mismatched unrelated donors in Japanese patients. Patients were administered bortezomib on days 1, 4, and 7, with short-term methotrexate and tacrolimus. Three bortezomib dose levels were prepared (1.0, 1.3, and 1.5 mg/m2). A dose of 1.3 mg/m2 was planned for administration to the initial six patients, and was adjusted if dose-limiting toxicity developed. Five of six patients enrolled for the initial d...
Source: International Journal of Hematology - September 27, 2019 Category: Hematology Authors: Nakane T, Okamura H, Tagaito Y, Koh S, Yoshimura T, Makuuchi Y, Nanno S, Nakamae M, Hirose A, Nakashima Y, Koh H, Hino M, Nakamae H Tags: Int J Hematol Source Type: research

Effect of study-level factors on treatment-free remission rate in patients with chronic myeloid leukemia: a systematic review and meta-analysis.
Abstract As it is recommended that most assessments for treatment-free remission (TFR) in patients with chronic myeloid leukemia be conducted as prospective trials, we conducted a systematic review and meta-analysis to investigate which study-level factors affected the TFR rate. The MEDLINE, Embase, and Cochrane databases were systematically searched from inception to July 2018. A random effect model was used to estimate the overall mean TFR rate, subgroup differences, and regression coefficients with continuous variables. Overall, 12 tyrosine kinase inhibitor (TKI) stopping studies comprising 1699 chronic myeloid...
Source: International Journal of Hematology - September 27, 2019 Category: Hematology Authors: Kim J, Park J, Moon Y, Choi SJ, Lim JH, Lee MH, Cho J Tags: Int J Hematol Source Type: research

Donor single nucleotide polymorphism in ACAT1 affects the incidence of graft-versus-host disease after bone marrow transplantation.
Abstract Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1) is an enzyme that converts cholesterol to cholesteryl esters. A recent in vivo study reported that inhibiting ACAT1 enzyme activity upregulates the membrane cholesterol levels of T cells, enhancing their cytotoxic function. In the present study, we investigated whether the presence of the ACAT1 single nucleotide polymorphism rs11545566 in transplant donors affected the risk of graft-versus-host disease (GVHD) in 116 adult patients who underwent bone marrow transplantation from human leukocyte antigen-identical sibling donors, and who received GVH...
Source: International Journal of Hematology - September 26, 2019 Category: Hematology Authors: Kamoshita S, Murata M, Koyama D, Julamanee J, Okuno S, Takagi E, Miyao K, Goto T, Ozawa Y, Miyamura K, Terakura S, Nishida T, Kiyoi H Tags: Int J Hematol Source Type: research

Supportive care for hemostatic complications associated with pediatric leukemia: a national survey in Japan.
Abstract Optimal supportive care for disseminated intravascular coagulation (DIC) and hemostatic complications by asparaginase is indispensable for the successful treatment of pediatric leukemia. However, the situation regarding this type of care in Japan is unclear. We conducted a questionnaire-based survey at 155 institutions treating childhood leukemia in Japan. The questionnaire asked about the supportive care provided by each institution to acute leukemia patients with DIC and asparaginase-induced hemostatic alterations. Ninety-eight institutions responded. The most common diagnostic criteria for DIC were tho...
Source: International Journal of Hematology - September 26, 2019 Category: Hematology Authors: Osone S, Fukushima K, Yano M, Kakazu M, Sano H, Kato Y, Shinkoda Y, Shinoda K, Mori N, Adachi S Tags: Int J Hematol Source Type: research

Analysis of glutathione S-transferase and cytochrome P450 gene polymorphism in recipients of dose-adjusted busulfan-cyclophosphamide conditioning.
Abstract Sporadic incidence of veno-occlusive disease (VOD) continues to occur, despite achievement of recommended busulfan (BU) concentrations after real-time BU dose adjustment. To explore the potential influence of glutathione S-transferase (GST) and cytochrome P450 (CYP) genotypes on plasma BU concentration, subsequent VOD, and transplant outcome, we assessed the polymorphisms of multiple GST and CYP genes. Fifty-five patients were included (median age 38 years; range 21-67). Of these, 49 received dose-adjusted BU/CY therapy. Twenty-six patients received transplants from human leukocyte antigen-identical ...
Source: International Journal of Hematology - September 25, 2019 Category: Hematology Authors: Terakura S, Onizuka M, Fukumoto M, Kuwatsuka Y, Kohno A, Ozawa Y, Miyamura K, Inagaki Y, Sawa M, Atsuta Y, Suzuki R, Naoe T, Morishita Y, Murata M, Nagoya Blood and Marrow Transplantation Group Tags: Int J Hematol Source Type: research

Promyelocyte-like blasts in B-lymphoblastic leukemia of a 67-year-old male patient.
PMID: 31555970 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
Source: International Journal of Hematology - September 25, 2019 Category: Hematology Authors: Ma Y, Leng Q, Zhao Y, Wang E Tags: Int J Hematol Source Type: research

Prognostic factors for survival of herpes simplex virus-associated hemophagocytic lymphohistiocytosis.
Abstract Hemophagocytic lymphohistiocytosis (HLH) occurs in neonates with disseminated infection of herpes simplex virus (HSV). Little has been reported on the control of rapid HLH progression. We studied the cytokine profile and genetic basis of two index cases with divergent outcomes after early treatment of type 2 HSV infection. One survivor had fever and elevated serum levels of tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), interferon (IFN)-β, and IFN-γ at diagnosis. The other neonate had no fever or TNF-α production, but significant IL-6 or IFN responses during the treatment cour...
Source: International Journal of Hematology - September 23, 2019 Category: Hematology Authors: Sonoda M, Ishimura M, Eguchi K, Shiraishi A, Kanno S, Kaku N, Inoue H, Motomura Y, Ochiai M, Sakai Y, Nakayama M, Ohara O, Ohga S Tags: Int J Hematol Source Type: research

Evaluation of a biosimilar granulocyte colony-stimulating factor for peripheral blood stem cell mobilization in Japanese healthy donors: a prospective study.
Abstract A "biosimilar" is a biotechnological product with a lower cost profile and equivalent efficacy and safety to the originator, but post-marketing clinical evaluation of biosimilar products has not been adequately conducted. We prospectively investigated the utility of biosimilar filgrastim in 13 peripheral blood stem cell (PBSC) donors from June 2014 to January 2017. In addition, we retrospectively compared these to another 13 PBSC donors mobilized with the originator filgrastim in the same period. Donor characteristics were equivalent between the groups. The median number of CD34+ cells per donor...
Source: International Journal of Hematology - September 21, 2019 Category: Hematology Authors: Sato K, Ishiyama K, Aoki G, Maruyama H, Tsuji N, Tanabe M, Zaimoku Y, Sato H, Yamazaki H, Yamaguchi M, Takami A, Nakao S Tags: Int J Hematol Source Type: research

A case of AL amyloidosis associated with follicular lymphoma with plasmacytic differentiation.
Abstract A 58-year-old woman underwent emergency surgical resection of the small intestine for intussusception as diagnosed at our hospital. Histopathological diagnosis of the resected specimen of the ileum was amyloid light chain (AL) amyloidosis. The colonoscopy after the surgical resection and following histopathological analysis of the biopsied specimens of the colon revealed follicular lymphoma (FL) grade 1 with plasmacytic differentiation. Histological findings of these ileal and colonic lesions were characteristic. In the ileum, CD10-positive lymphoid follicles and CD38-positive interfollicular plasma cell ...
Source: International Journal of Hematology - September 21, 2019 Category: Hematology Authors: Matsumoto Y, Masuda T, Nishimura A, Horie H, Harada K, Yoshida M, Shimura K, Kaneko H, Taniwaki M Tags: Int J Hematol Source Type: research

Loss of nivolumab binding to T cell PD-1 predicts relapse of Hodgkin lymphoma.
Abstract Nivolumab is effective in the treatment of classical Hodgkin lymphoma that relapsed after allogeneic hematopoietic stem cell transplantation (SCT) with the risk of graft-versus-host disease; however, the optimal time and dose of nivolumab administration remain to be investigated. Nivolumab binding to PD-1 masks flowcytometric detection of PD-1 by the anti-PD-1 monoclonal antibody EH12.1. Using this method, we monitored nivolumab binding on T cells after nivolumab treatment in a patient with classical Hodgkin lymphoma relapsed after allogeneic SCT. Nivolumab was effective while prolonged nivolumab binding ...
Source: International Journal of Hematology - September 19, 2019 Category: Hematology Authors: Ogasawara R, Hashimoto D, Sugita J, Yamawaki F, Naka T, Mitsuhashi T, Takahashi S, Miyashita N, Okada K, Onozawa M, Matsuno Y, Teshima T Tags: Int J Hematol Source Type: research

Successful management of fetal hemolytic disease due to strong anti-Rh17 with plasma exchange and intrauterine transfusion in a woman with the D--  phenotype.
We report successful management of a pregnancy associated with fetal hemolytic disease owing to high titers of anti-Rh17 (1:4096) in a woman with a history of a pregnancy with fetal hydrops and intrauterine fetal death. During her second pregnancy, she received two sets of plasma exchange (PE) per week from weeks 12 till 20. Intrauterine transfusions (IUTs) were performed at 26, 27, 29, and 31 weeks. A male infant was born at 32 weeks and 4 days by normal vaginal delivery, with a birth weight of 1916 g (+ 0.16 SD). He received an exchange transfusion on day 0, immunoglobulin (intravenous immunoglob...
Source: International Journal of Hematology - September 19, 2019 Category: Hematology Authors: Mimura K, Endo M, Takahashi A, Doi Y, Sakuragi M, Kiyokawa T, Taniguchi H, Kitabatake Y, Handa M, Tomimatsu T, Tomiyama Y, Isaka Y, Kimura T Tags: Int J Hematol Source Type: research

Cessation of nilotinib in patients with chronic myelogenous leukemia who have maintained deep molecular responses for 2 years: a multicenter phase 2 trial, stop nilotinib (NILSt).
Abstract The aim of this multicenter phase 2 trial, Stop Nilotinib (NILSt), was to examine the safety and efficacy of discontinuation of nilotinib in patients with chronic phase (CP)-chronic myelogenous leukemia (CML). Patients with CP-CML who had achieved molecular response (MR4.5) after initiation of imatinib or nilotinib therapy received consolidation therapy with nilotinib 300-400 mg twice daily for up to 24 months. Patients who maintained MR4.5 at 24 months of consolidation therapy proceeded to discontinuation of nilotinib. The study enrolled 149 patients; 112 patients proceeded to consolidatio...
Source: International Journal of Hematology - September 19, 2019 Category: Hematology Authors: Nagafuji K, Matsumura I, Shimose T, Kawaguchi T, Kuroda J, Nakamae H, Miyamoto T, Kadowaki N, Ishikawa J, Imamura Y, Yamazaki H, Akashi K, Kanakura Y Tags: Int J Hematol Source Type: research

Persistent clonal cytogenetic abnormality with del(20q) from an initial diagnosis of acute promyelocytic leukemia.
Abstract A 68-year-old male was diagnosed with acute promyelocytic leukemia (APL). A G-banding chromosomal analysis revealed the co-existence of two clones: one with del(20q) and t(15;17)(q22;q12) and another with del(20q) alone. During the remission of APL following treatment with all-trans-retinoic acid, del(20q) was persistently identified, indicating a diagnosis of cytogenetic abnormalities of undetermined significance (CCAUS) with isolated del(20q). Bicytopenia developed 48 months after the remission of APL. The presence of isolated del(20q) was detected in the G-banding analysis, whereas morphological d...
Source: International Journal of Hematology - September 12, 2019 Category: Hematology Authors: Fujioka M, Itonaga H, Kato T, Nannya Y, Hashimoto M, Kasai S, Toriyama E, Kamijo R, Taguchi M, Taniguchi H, Sato S, Atogami S, Imaizumi Y, Hata T, Moriuchi Y, Ogawa S, Miyazaki Y Tags: Int J Hematol Source Type: research

JSH practical guidelines for hematological malignancies, 2018: II. Lymphoma-3. Lymphoplasmacytic lymphoma/Waldenstr öm's macroglobulinemia (LPL/WM).
JSH practical guidelines for hematological malignancies, 2018: II. Lymphoma-3. Lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM). Int J Hematol. 2019 Sep 07;: Authors: Kobayashi Y PMID: 31494831 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
Source: International Journal of Hematology - September 7, 2019 Category: Hematology Authors: Kobayashi Y Tags: Int J Hematol Source Type: research

Cryoglobulinemic vasculitis with interruption of ibrutinib therapy for chronic lymphocytic leukemia (CLL).
Abstract Chronic lymphocytic leukemia (CLL) can trigger autoimmune phenomena, with immune thrombocytopenia (ITP) the most common presentation. Upon cessation of CLL therapy, including ibrutinib, autoimmune flares can occur. In a 68-year-old man with CLL, ibrutinib was held for 2 weeks prior to elective shoulder surgery. Eleven days after stopping therapy, he presented with a purpuric rash on his right hip, buttock, and lower extremities. He experienced two episodes of seizure activity while hospitalized. MRI brain demonstrated patchy areas of altered signal involving deep white matter and sub-cortical white matter...
Source: International Journal of Hematology - September 7, 2019 Category: Hematology Authors: Wright N, Voshtina E, George G, Singavi A, Field J Tags: Int J Hematol Source Type: research

Efficacy and safety of quizartinib in Japanese patients with FLT3-ITD positive relapsed or refractory acute myeloid leukemia in an open-label, phase 2 study.
Abstract FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations in patients with acute myeloid leukemia (AML) are associated with early relapse and poor survival. This multicenter, single-arm, two-stage phase 2 study (NCT02984995) was conducted to evaluate the efficacy and safety of quizartinib hydrochloride (initial dose 20/30 mg/day), an oral, highly potent, selective FLT3 inhibitor in Japanese patients (median age 65 years) with FLT3-ITD positive relapsed/refractory (R/R) AML. The composite complete remission (CRc) rate (primary endpoint) was 53.8% (90% confidence interval 36.2-...
Source: International Journal of Hematology - August 31, 2019 Category: Hematology Authors: Takahashi T, Usuki K, Matsue K, Ohno H, Sakura T, Imanaka R, Murakami M, Ohwada S, Takagi T, Sakajiri S Tags: Int J Hematol Source Type: research

CCR4 is rarely expressed in CCR4-mutated T/NK-cell lymphomas other than adult T-cell leukemia/lymphoma.
This study suggests that frequencies of CCR4 expression and genomic CCR4 mutations and an association between the two may be considerably different between ATL cases and non-ATL T/NK-cell lymphomas. PMID: 31468320 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
Source: International Journal of Hematology - August 29, 2019 Category: Hematology Authors: Sakamoto Y, Fujii K, Murase S, Nakano S, Masaki A, Murase T, Kusumoto S, Iida S, Utsunomiya A, Ueda R, Ishida T, Inagaki H Tags: Int J Hematol Source Type: research

Comprehensive prognostic scoring systems could improve the prognosis of adult acute myeloid leukemia patients.
Abstract Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by a dismal outcome. To enable better outcomes, it is necessary to develop individual therapies based on risk stratification. In the present study, we established two new comprehensive prognostic scoring systems (CPSS) for overall survival (OS) and relapse-free survival (RFS) using the Cox proportional hazards regression, CPSS integrated and weighted age, AML type, lactic dehydrogenase (LDH), ECOG score, cytogenetics, and gene mutations. We divided patients into three risk groups-low-, intermediate-, and high-risk-with 1-year OS rate...
Source: International Journal of Hematology - August 22, 2019 Category: Hematology Authors: Zhou F, Zhou F, Du M, Liu L, Guo T, Xia L, Jin R, Hu Y, Mei H Tags: Int J Hematol Source Type: research

Significance of FLT3-tyrosine kinase domain mutation as a prognostic factor for acute myeloid leukemia.
Marumo A, Omori I, Fujiwara Y, Terada K, Yui S, Wakita S, Arai K, Kitano T, Kakihana K, Kanda Y, Ohashi K, Fukuda T, Inokuchi K Abstract The prognostic significance of FLT3-tyrosine kinase domain (TKD) mutations remains unknown. To investigate the prognostic impact of FLT3-TKD, 676 de novo acute myeloid leukemia (AML), we retrospectively analyzed cases and conducted a review of the literature. Of the 676 de novo AML cases, 34 (5.0%) were FLT3-TKD-positive; both FLT3-TKD and FLT3-ITD were noted in only two cases (0.3%). Although no significant differences in relapse-free survival (RFS) were noted, FLT3-TKD-positiv...
Source: International Journal of Hematology - August 20, 2019 Category: Hematology Authors: Sakaguchi M, Yamaguchi H, Kuboyama M, Najima Y, Usuki K, Ueki T, Oh I, Mori S, Kawata E, Uoshima N, Kobayashi Y, Kako S, Tajika K, Shono K, Kayamori K, Hagihara M, Kanda J, Uchiyama H, Kuroda J, Uchida N, Kubota Y, Kimura S, Kurosawa S, Date K, Nakajima N Tags: Int J Hematol Source Type: research

BCR-ABL induces tyrosine phosphorylation of YAP leading to expression of Survivin and Cyclin D1 in chronic myeloid leukemia cells.
Abstract In the present study, we studied downstream signals of BCR-ABL with regard to Src family kinases and YAP, a transcription cofactor and an effector of the Hippo pathway. We first checked the phosphorylation status of YAP and found that it was constitutively phosphorylated at tyrosine 357 in CML-derived cell lines (TCC-S and K562) but not in AML-derived cell lines (HL-60 and KG-1a). Treatment with imatinib or RK-20449 inhibited cell growth and decreased tyrosine phosphorylation of YAP in both CML lines. Expression of Survivin or Cyclin D1 was decreased in TCC-S, but not in either HL-60 or KG-1a. Furthermore...
Source: International Journal of Hematology - August 19, 2019 Category: Hematology Authors: Moriyama K, Hori T Tags: Int J Hematol Source Type: research

Essential thrombocytosis attributed to JAK2-T875N germline mutation.
Abstract The aim of this study was to elucidate the role of a non-canonical JAK2 mutation JAK2-T875N, which was identified by exome sequencing in a patient with essential thrombocytosis (ET) who had a family history of suspecting ET. Whole exome sequencing was performed on peripheral blood mononuclear cells and buccal swab-derived genomic DNA. Sanger sequencing was performed to confirm the variant. We evaluated the function of the mutation on JAK2 activity and downstream signaling (Erk, STATs) using JAK2-T875N-transfected or transduced cell lines. 293T cells transfected with JAK2 cDNA carrying V617F or T875N mutat...
Source: International Journal of Hematology - August 19, 2019 Category: Hematology Authors: Yoshimitsu M, Hachiman M, Uchida Y, Arima N, Arai A, Kamada Y, Shide K, Ito M, Shimoda K, Ishitsuka K Tags: Int J Hematol Source Type: research

JSH practical guidelines for hematological malignancies, 2018: II. Lymphoma-2. Marginal zone lymphoma (MALT lymphoma/extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue and splenic marginal zone lymphoma).
PMID: 31428970 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
Source: International Journal of Hematology - August 19, 2019 Category: Hematology Authors: Kobayashi Y Tags: Int J Hematol Source Type: research

FF-10501 induces caspase-8-mediated apoptotic and endoplasmic reticulum stress-mediated necrotic cell death in hematological malignant cells.
Abstract FF-10501 is a novel inhibitor of inosine monophosphate dehydrogenase (IMPDH). Clinical trials of FF-10501 for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are currently being conducted in the United States. Although it has been shown that FF-10501 induces apoptosis in hematological malignant cells, the intracellular mechanisms of this effect have not been characterized. We conducted an in vitro study to elucidate the mechanisms of FF-10501-induced cell death using 12 hematological malignant cell lines derived from myeloid and lymphoid malignancies. FF-10501 suppressed the growth of eac...
Source: International Journal of Hematology - August 12, 2019 Category: Hematology Authors: Matsumoto T, Jimi S, Migita K, Terada K, Mori M, Takamatsu Y, Suzumiya J, Hara S Tags: Int J Hematol Source Type: research

Prediction of clinical outcome by controlling nutritional status (CONUT) before allogeneic hematopoietic stem cell transplantation in myeloid malignancies.
Abstract Malnutrition before allogeneic hematopoietic cell transplantation (allo-HCT) is associated with poor clinical outcomes. Herein, we evaluated the predictive value of controlling nutritional status (CONUT) in patients undergoing allo-HCT for myeloid malignancies. We retrospectively analyzed 200 patients with myeloid malignancies who underwent allo-HCT for the first time. We evaluated CONUT before the initiation of conditioning and compared malnourished patients (poor CONUT, n = 56) with non-malnourished patients (normal CONUT, n = 144). The cumulative incidence of non-relapse mor...
Source: International Journal of Hematology - August 12, 2019 Category: Hematology Authors: Araie H, Kawaguchi Y, Okabe M, Lee Y, Ohbiki M, Osaki M, Goto M, Goto T, Morishita T, Ozawa Y, Miyamura K Tags: Int J Hematol Source Type: research

Osteosclerotic myeloma without features of POEMS syndrome.
PMID: 31407256 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
Source: International Journal of Hematology - August 12, 2019 Category: Hematology Authors: Terao T, Matsue K Tags: Int J Hematol Source Type: research

Vitamin B6 deficiency is prevalent in primary and secondary myelofibrosis patients.
Abstract Vitamin B6 (VB6) deficiency contributes to oncogenesis and tumor progression in certain cancers, and is prevalent in cancer patients in general. VB6 is also an essential element of heme synthesis, and deficiency can lead to anemia. Primary myelofibrosis (PMF) and secondary myelofibrosis (sMF) are myeloproliferative neoplasms often presenting with anemia along with other cytopenias. We performed a prospective study to determine whether PMF and sMF patients suffer from VB6 deficiency, and whether VB6-deficient patients show improvement of anemias with VB6 supplementation. Twelve PMF patients and 11 sMF pati...
Source: International Journal of Hematology - August 12, 2019 Category: Hematology Authors: Yasuda H, Tsutsui M, Ando J, Inano T, Noguchi M, Yahata Y, Tanaka M, Tsukune Y, Masuda A, Shirane S, Misawa K, Gotoh A, Sato E, Aritaka N, Sekiguchi Y, Sugimoto K, Komatsu N Tags: Int J Hematol Source Type: research

Study of pathophysiology and molecular characterization of congenital anemia in India using targeted next-generation sequencing approach.
Abstract Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes that are involved in rare anemias, due to similarities in the clinical presentation. We sought to enhance the diagnosis of patients with congenital anemias by using targeted next-generation sequencing. The genetic diagnosis was performed by gene capture followed by next-generation sequencing of 76 genes known to cause anemia synd...
Source: International Journal of Hematology - August 10, 2019 Category: Hematology Authors: Kedar PS, Harigae H, Ito E, Muramatsu H, Kojima S, Okuno Y, Fujiwara T, Dongerdiye R, Warang PP, Madkaikar MR Tags: Int J Hematol Source Type: research

Bortezomib-containing therapy in Japanese children with relapsed acute lymphoblastic leukemia.
Abstract Outcomes of children treated for relapsed acute lymphoblastic leukemia (ALL) remain poor. Bortezomib (BZM), a proteasome inhibitor, has shown promising activity against lymphoid malignancies. We conducted a phase I study to evaluate the safety and tolerability of multidrug chemotherapy including BZM in Japanese children with relapsed ALL. Three of five children with relapsed ALL enrolled in the study between November 2014 and April 2016 were evaluated. BZM (1.3 mg/m2) was administered on days 8, 11, 15, and 18 of multidrug induction chemotherapy. Pharmacokinetic studies were performed. Age at study e...
Source: International Journal of Hematology - August 10, 2019 Category: Hematology Authors: Hasegawa D, Yoshimoto Y, Kimura S, Kumamoto T, Maeda N, Hara J, Kikuta A, Kada A, Kimura T, Iijima-Yamashita Y, Saito AM, Horibe K, Manabe A, Ogawa C Tags: Int J Hematol Source Type: research

Chemotherapy-related nail toxicity.
PMID: 31401768 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
Source: International Journal of Hematology - August 10, 2019 Category: Hematology Authors: Antonioli E, Fani A, Sordi B, Puccini B, Bosi A Tags: Int J Hematol Source Type: research

Real-world data on the efficacy and safety of daratumumab treatment in Hungarian relapsed/refractory multiple myeloma patients.
ute;s Á, Mikala G, Váróczy L Abstract Daratumumab is a human anti-CD38 monoclonal antibody used in the treatment of refractory and relapsed multiple myeloma. We investigated the efficacy and safety of daratumumab therapy in a real-world setting. Ninety-nine Hungarian patients were included; 48 received monotherapy, while lenalidomide and bortezomib combinations were administered in 29 and 19 cases, respectively. Overall response rate was assessable in 88 patients, with 12 complete, 10 very good partial, 34 partial, and seven minor responses. At a median duration of follow-up of 18.6 month...
Source: International Journal of Hematology - August 7, 2019 Category: Hematology Authors: Lovas S, Varga G, Farkas P, Masszi T, Wohner N, Bereczki Á, Adamkovich N, Borbényi Z, Szomor Á, Alizadeh H, Szaleczky E, Wolf K, Schneider T, Plander M, Szendrei T, Csacsovszki O, Csukly Z, Rajnics P, Egyed M, Nagy Z, Rejtő L, Illés Á, Mikala G, Vá Tags: Int J Hematol Source Type: research

Outcomes for Asian patients with multiple myeloma receiving once- or twice-weekly carfilzomib-based therapy: a subgroup analysis of the randomized phase 3 ENDEAVOR and A.R.R.O.W. Trials.
Abstract Carfilzomib is an irreversible proteasome inhibitor used for the treatment of relapsed and/or refractory multiple myeloma (RRMM). We evaluated the efficacy and safety of carfilzomib in subgroups of Asian patients in the randomized phase 3 ENDEAVOR and A.R.R.O.W. trials. In ENDEAVOR, patients received carfilzomib twice-weekly (56 mg/m2) plus dexamethasone (Kd; n = 56) or bortezomib plus dexamethasone (Vd; n = 57). In A.R.R.O.W., patients received carfilzomib once-weekly (70 mg/m2, n = 30) or twice-weekly (27 mg/m2, n = 15) plus dexameth...
Source: International Journal of Hematology - August 6, 2019 Category: Hematology Authors: Dimopoulos MA, Moreau P, Iida S, Huang SY, Takezako N, Chng WJ, Zahlten-Kumeli A, Sersch MA, Li J, Huang M, Lee JH Tags: Int J Hematol Source Type: research

Safety and pharmacokinetics of quizartinib in Japanese patients with relapsed or refractory acute myeloid leukemia in a phase 1 study.
Abstract Expanded therapeutic options are warranted for patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) who have FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations. The present phase 1, multicenter, open-label, dose-escalation and dose-expansion study was conducted to assess the safety, pharmacokinetics, and efficacy of multiple-dose monotherapy of the FLT3 inhibitor, quizartinib, in Japanese patients with R/R AML. Patients received oral quizartinib, once daily, under fasting conditions in 28-day cycles. Sixteen patients (median age, 68.0 years; male, 56.3%; FL...
Source: International Journal of Hematology - July 29, 2019 Category: Hematology Authors: Usuki K, Handa H, Choi I, Yamauchi T, Iida H, Hata T, Ohwada S, Okudaira N, Nakamura K, Sakajiri S Tags: Int J Hematol Source Type: research

Serum ferritin levels at diagnosis predict prognosis in patients with low blast count myelodysplastic syndromes.
pathic Bone Marrow Failure Syndromes Abstract Serum ferritin, a marker of systemic iron status, is considered a prognostic factor for patients with myelodysplastic syndromes (MDS), despite the lack of supporting evidence. We investigated the association between serum ferritin levels at diagnosis and the prognoses of Japanese MDS patients with bone marrow blasts 
Source: International Journal of Hematology - July 29, 2019 Category: Hematology Authors: Kawabata H, Usuki K, Shindo-Ueda M, Kanda J, Tohyama K, Matsuda A, Araseki K, Hata T, Suzuki T, Kayano H, Shimbo K, Chiba S, Ishikawa T, Arima N, Nohgawa M, Miyazaki Y, Kurokawa M, Arai S, Mitani K, Takaori-Kondo A, Japanese National Research Group on Idi Tags: Int J Hematol Source Type: research

Discrepancy in the degree of polycythemia in a family with a novel nonsense EPOR mutation.
PMID: 31347091 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
Source: International Journal of Hematology - July 26, 2019 Category: Hematology Authors: Ratarat C, Ittiwut C, Natesirinilkul R, Sathitsamitpong L, Fanhchaksai K, Charoenkwan P, Suphapeetiporn K, Shotelersuk V Tags: Int J Hematol Source Type: research

Successful treatment with 2-chlorodeoxyadenosine of refractory pediatric Langerhans cell histiocytosis with initial involvement of the gastrointestinal tract.
Abstract Gastrointestinal (GI) tract involvement in Langerhans cell histiocytosis (LCH) is extremely rare. Langerhans cell histiocytosis with GI tract involvement (GI-LCH) is frequently associated with multi-system disease, and usually presents with severe systemic symptoms, such as protein-losing enteropathy (PLE). Although the GI tract is not included among the organs at risk, the prognosis of GI-LCH is poor, and no effective chemotherapeutic regimen has been identified. Here, we report an infant case of primary refractory GI-LCH with PLE that showed marked improvement in response to 2-chlorodeoxyadenosine (2-Cd...
Source: International Journal of Hematology - July 26, 2019 Category: Hematology Authors: Mayumi A, Imamura T, Sakamoto K, Ota T, Osone S, Usami I, Hosoi H Tags: Int J Hematol Source Type: research

A less-intensive anticoagulation protocol of therapeutic unfractionated heparin administration for pregnant patients.
Abstract Heparin anticoagulant therapy for thromboembolic disorders during pregnancy is problematic due to unexpected adverse bleeding. To avoid bleeding, we have used a less-intensive anticoagulation protocol of unfractionated heparin (UFH). The protocol had a therapeutic activated partial thromboplastin time (APTT) ratio of 1.5-2.0 with the control value, a UFH dose of ≤ 30,000 U/day, and an antithrombin (AT) activity target of ≥ 70%. In the present study, we evaluated this protocol using an anti-Xa assay. We collected UFH-treated plasma samples from ten consecutive pregnan...
Source: International Journal of Hematology - July 25, 2019 Category: Hematology Authors: Neki R, Mitsuguro M, Okamoto A, Ida K, Miyoshi T, Kamiya C, Iwanaga N, Miyata T, Yoshimatsu J Tags: Int J Hematol Source Type: research

Tetrasomy 8 and isochromosome 7q in CD5-positive hepatosplenic T-cell lymphoma with leukemic presentation.
PMID: 31342408 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
Source: International Journal of Hematology - July 24, 2019 Category: Hematology Authors: Yamamoto K, Yakushijin K, Okuni-Watanabe M, Hashimoto A, Matsuoka H, Minami H Tags: Int J Hematol Source Type: research

Unusual computed tomography findings of acute eosinophilic pneumonia after cord blood transplantation.
PMID: 31325151 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
Source: International Journal of Hematology - July 19, 2019 Category: Hematology Authors: Senjo H, Hashimoto D Tags: Int J Hematol Source Type: research

Report of phase I and II trials of melphalan, prednisolone, and thalidomide triplet combination therapy versus melphalan and prednisolone doublet combination therapy in Japanese patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplantation.
Abstract We conducted a phase I study to determine the recommended dose of thalidomide combined with melphalan plus prednisolone (MPT) and a phase II study evaluating the efficacy and safety of this MPT regimen in transplant-ineligible Japanese patients with untreated multiple myeloma. The recommended dose was determined to be 100 mg/day in the phase I study. In the phase II, randomized, double-blind, parallel-group study, patients were allocated to either MPT (n = 52) or MP (n = 51), with 21 and 29 patients completing the study, respectively. Overall response rate, the primary end...
Source: International Journal of Hematology - July 19, 2019 Category: Hematology Authors: Suzuki K, Doki N, Meguro K, Sunami K, Kosugi H, Sasaki O, Takagi T, Murakami H, Shimizu K Tags: Int J Hematol Source Type: research