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Elotuzumab-based regimens are sometimes selected for multiple myeloma treatment after daratumumab-based regimens. However, there has been insufficient discussion on the efficacy of elotuzumab after daratumumab. We used Kansai Myeloma Forum registration data in a multicenter retrospective evaluation of the efficacy of elotuzumab after daratumumab. Overall survival (OS) rate and time to next treatment (TTNT) were significantly worse in the cohort given elotuzumab after daratumumab (Dara cohort, n = 47) than in the cohort with no history of daratumumab administration before elotuzumab (No-Dara cohort, n = 80, OS: P = 0.03; TTNT: P = 0.02; best response: P < 0.01). In the Dara cohort, OS and TTNT rates were worse with sequential elotuzumab use after daratumumab than with non-sequential (OS: P = 0.02; TTNT: P = 0.03). In patients given elotuzumab < 180 days after daratumumab, OS (P = 0.08) and best response (P = 0.21) tended to be worse, and TTNT was significantly worse (P = 0.01), than in those given elotuzumab after ≥ 180 days. These findings were confirmed by subgroup analyses and multivariate analyses. Monoclonal-antibody-free treatment might be preferable after daratumumab-based regimens. If possible, elotuzumab-based regimens should be considered only ≥ 180 days after daratumumab use. [ABSTRACT FROM AUTHOR]

• Absence of KIR2DL1 ligands increases relapse in HLA-matched hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia (ALL). • This trend is prominent in patients with Ph-negative ALL who experienced acute graft-versus-host disease. • The trend is the opposite of that in our previous report analyzing HSCT for acute myeloid leukemia/chronic myeloid leukemia. Natural killer (NK) cells expressing killer cell immunoglobulin-like receptors (KIRs) can recognize specific HLA class I molecules as their ligands. By studying a large Japanese transplant registry, we compared transplant outcomes between patients heterozygous for HLA-CAsn80/CLys80 (HLA-C1/C2) and those homozygous for HLA-C1 (HLA-C1/C1) among patients who had undergone HLA-matched hematopoietic stem cell transplantation (HSCT). A high frequency of KIR2DL1 with strong HLA-C2 binding capacity and a low frequency of HLA-C2 and KIR haplotype B are characteristic of the Japanese population. In our previous report, HLA-C1/C1 patients with myeloid leukemia were less likely to relapse than HLA-C1/C2 patients. We newly assessed 2884 patients with acute lymphoblastic leukemia (ALL) who received HLA-matched allogeneic HSCT and analyzed their leukemia relapses by using adjusted competing-risk methods. HLA-C1/C1 patients with ALL experienced significantly higher relapse rates than HLA-C1/C2 patients (hazard ratio [HR] = 1.55, P =.003), contrary to our results in patients with myeloid leukemia. We allocated patients with ALL to several subgroups and found a higher frequency of relapse (HR >1.8) in the HLA-C1/C1 group than in the HLA-C1/C2 group among patients with Ph-negative ALL, those who had no cytomegalovirus reactivation, those who received transplants from donors who were aged 41 years or older, and those who experienced acute graft-versus-host disease, especially if it required systemic treatment. One interpretation of our results is that KIR2DL1-positive NK cells disrupt T cells, antigen-presenting cells, or both from working efficiently in transplant immunity in HLA-C1/C1 patients with ALL. Another is that KIR2DS1-positive NK cells directly attack HLA-C2-positive ALL blasts in HLA-C1/C2 patients. Whether HLA-C2 can cause recurrence to decrease or increase in patients depending on the disease (ALL or myeloid leukemia) will be a very important finding. We hope that our results will provide clues to the real mechanisms behind relapse after transplantation in patients with different HLA profiles. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells assume graft-versus-leukemia alloreactivity after hematopoietic stem cell transplantation (HSCT) through their inhibitory killer cell immunoglobulin-like receptors (KIRs). KIR2D family members recognize HLA-C alleles with Asn80 (HLA-C1) or Lys80 (HLA-C2). The predominance of HLA-C1 over HLA-C2 and the frequent presence of KIR2DL1 are characteristic of Japanese people. We compared clinical outcomes among homozygous HLA-C1 (HLA-C1/C1) patients and heterozygous HLA-C1/C2 patients who underwent HLA-matched HSCT for hematologic malignancies by assessing the data of 10,638 patients from the Japanese national registry. HLA-C1/C1 recipients had a lower rate of relapse than HLA-C1/C2 recipients after transplantation for acute myelogenous leukemia (AML) (hazard ratio [HR], .79; P  = .006) and chronic myelogenous leukemia (CML) (HR, .48; P  = .025), but not for acute lymphoblastic leukemia (HR, 1.36), lymphoma (HR, .97), or low-grade myelodysplastic syndrome (HR, 1.40). We then grouped AML and CML patients together and divided them into several subgroups. Advantages of HLA-C1/C1 recipients over HLA-C1/C2 recipients regarding relapse were observed irrespective of donor relation (related: HR, .79, P  = .069; unrelated: HR, .77, P  = .022), preparative regimen (myeloablative: HR, .79, P  = .014; reduced intensity: HR, .73, P  = .084), and occurrence of acute graft-versus-host disease (yes: HR, .70, P  = .122; no, HR .71, P  = .026) or cytomegalovirus reactivation (reactivated: HR .67, P  = .054; nonreactivated: HR .71, P  = .033); however, these advantages were not observed in recipients with a delay in achieving complete chimerism (HR, 1.06). The advantage of decreasing relapse and extending relapse-free survival of C1/1 over C1/2 KIR-ligand status was most pronounced in T cell-depleted HSCT (HR, .27; P  < .001 and HR, .30; P  = .002, respectively) and in children age <15 years (HR, .29; P  < .001 and HR .31; P  < .001, respectively). Our findings represent an important mechanism responsible for the immunity against HLA-C2–negative myeloid leukemia cells after HLA-matched transplantation. [ABSTRACT FROM AUTHOR]

Licensing by self MHC class I ligands is required for proper natural killer (NK) cell response. NK cells with inhibitory killer cell immunoglobulin-like receptors for nonself MHC exhibit transient alloreactivity after hematopoietic stem cell transplantation (HSCT). We analyzed 3866 recipients in the Japan national registry who underwent their first allogeneic HSCT for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) from HLA-A, -B, and -DRB1 allele-genomatched unrelated donors. By classifying them into 5 independent groups based on HLA-C group matching and assumed donor NK cell status, we found that for HLA-C–matched HSCT for AML in HLA-C1/C1 recipients, in whom transient alloreactivity against HLA-C2–negative leukemic cells was expected, the relapse rate was significantly lower than it was in HLA-C–matched HSCT for AML in HLA-C1/C2 recipients (hazard ratio [HR], .72; P = .011). This difference was not observed in HLA-C–matched HSCT for ALL. Compared with HLA-C–matched HSCT, significantly higher mortality was observed in HLA-C1/C1 AML patients who received transplants from HLA-C–mismatched HLA-C1/C1 donors (HR, 1.37; P = .001) and in HLA-C1/C1 ALL patients who received transplants from HLA-C2–positive donors (HR, 2.13; P = .005). In conclusion, donor selection based on leukemic subtype and donor HLA-C group matching improves transplantation outcome after HLA-C–mismatched HSCT. [ABSTRACT FROM AUTHOR]

Background aims. Cell therapy with mesenchymal stromal cells (MSC) has been reported recently as a promising treatment for severe acute graft-versus-host disease (GvHD). Methods. We designed a pilot study to treat severe hepatic or gut GvHD using MSC derived from only the donor and cultured without bovine serum. Because the number of cultured MSC is smaller using this method, we planned to treat patients by intra-arterial regional administration directly to the target organs. Results. Three patients were enrolled, and the MSC could be expanded using donor serum. There were no obvious side-effects immediately after arterial injection. The maximum response was partial in one of three patients and did not continue for more than 2 months. Idiopathic pneumonia syndrome developed in two of the three patients. Conclusions. A single local arterial MSC injection was unable to save these patients’ lives and so might not be more effective than multiple systemic intravenous MSC injection. Further clinical research and additional strategies are required to develop appropriate methods for using MSC to achieve extended remission of GvHD. [ABSTRACT FROM AUTHOR]

• Various humoral factors and cell contacts can activate NK cells, but signals from inhibitory receptors often overcome them. • The significance of HLAs and their cognate inhibitory KIRs in transplant donors and recipients is drawing attention. • Japanese transplant registry for leukemia shows the merits and demerits depending on the presence of KIR2DL1-ligands. Natural killer (NK) cells were originally considered to belong to the innate immune system to play a protective role against tumor cells and viral infections. In human, they can recognize self and non-self HLA class 1 as their ligand. So, analyzing the outcomes of allogeneic hematopoietic stem cell transplantation is a good opportunity to know the antitumor effects and regulatory effects of NK cells through HLA class 1 matching and mismatching of donor and recipient. In this review, I looked back on the main analysis results of the past transplants, summarized our reports consisting of many cases in a single ethnic, and showed that NK cells might work oppositely depending on the type of leukemia. New treatment strategies based on these concepts may offer individualized treatment options and ultimately increase offer the possibility of a cure for patients with leukemia. [ABSTRACT FROM AUTHOR]

Summary. A 69-year-old man presented with right neck tumour. Primary thyroid MALT lymphoma occurring in Hasimoto's thyroiditis was diagnosed. He was also diagnosed to have gastric cancer with Helicobacter pylori infection. After subtotal gastrectomy by itself, thyroid lymphoma became smaller transiently. Then the patient was treated with H. pylori eradication therapy, resulting in the complete disappearance of lymphoma. Although H. pylori organisms were not detected in the lymphoma tissue by polymerase chain reaction (PCR), it might be implicated in the pathogenesis of extragastric MALT lymphomas. [ABSTRACT FROM AUTHOR]

Knowledge of the SARS-CoV-2 antibody titers induced by tixagevimab–cilgavimab in patients with hematologic diseases remains insufficient. Here, we performed a single-center, prospective study to reveal the changes in antibody titer after administration of tixagevimab–cilgavimab in 78 patients with hematologic diseases. The median peak titer was 155.4 U/mL, and the median AUC was 46556 days·U/mL. First, we compared several characteristics between patients with low titers (peak titer ≤ 155.4 U/mL) and high titers (peak titer > 155.4 U/mL). We extracted 6 factors (patient age, sex, ECOG-PS, serum albumin level, and cross-sectional area and computed tomographic number of the psoas major muscle) as candidates influencing the antibody titers. Multiple regression analysis revealed that antibody titer was closely associated with these 6 factors (contribution rate = 0.76, p = 0.02). Our data support the inability of tixagevimab–cilgavimab to induce sufficient antibody titers against SARS-CoV-2, especially in older, frailer, female patients. [ABSTRACT FROM AUTHOR]

Summary: Morphological dysplasia in haematopoietic cells, defined by a 10% threshold in each lineage, is one of the diagnostic criteria for myelodysplastic neoplasms. Dysplasia limited to the erythroid lineage has also been reported in some cases of aplastic anaemia (AA); however, its significance remains unclear. We herein examined the impact of erythroid dysplasia on immunosuppressive therapy responses and survival in AA patients. The present study included 100 eligible AA patients without ring sideroblasts. Among them, 32 had dysplasia in the erythroid lineage (AA with minimal dysplasia [mini‐D]). No significant sex or age differences were observed between AA groups with and without erythroid dysplasia. In severe/very severe AA and non‐severe AA patients, a response to anti‐thymocyte globulin + ciclosporin within 12 months was observed in 80.0% and 60.0% of AA with mini‐D and 42.9% and 90.0% of those without dysplasia, with no significant difference (p = 0.29 and p = 0.24 respectively). Overall survival and leukaemia‐free survival did not significantly differ between the groups. Collectively, the present results indicate that the presence of erythroid dysplasia did not significantly affect clinical characteristics or outcomes in AA patients, suggesting that its presence in AA is acceptable. Therefore, erythroid dysplasia should not exclude an AA diagnosis. [ABSTRACT FROM AUTHOR]

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

Before autologous stem cell transplantation (ASCT), hematopoietic stem cells must be stimulated to move from the bone marrow to the peripheral blood for harvesting. Plerixafor, a C-X-C chemokine receptor type 4 antagonist, is used to increase stem cell harvests. However, the effects of plerixafor on post-ASCT outcomes remain unclear. In a dual-center retrospective cohort study of 43 Japanese patients who received ASCT, the authors compared transplantation outcomes in patients who underwent stem cell mobilization with granulocyte colony-stimulating factor with (n = 25) or without (n = 18) plerixafor. The number of days to neutrophil and platelet engraftment was significantly shorter with plerixafor than without plerixafor, as assessed by univariate (neutrophil, P = 0.004, platelet, P = 0.002), subgroup, propensity score matching and inverse probability weighting analyses. Although the cumulative incidence of fever was comparable with or without plerixafor (P = 0.31), that of sepsis was significantly lower with plerixafor than without (P < 0.01). Thus, the present data indicate that plerixafor leads to earlier neutrophil and platelet engraftment and a reduction of infectious risk. The authors conclude that plerixafor may be safe to use and that it reduces the risk of infection in patients with a low CD34+ cell count the day before apheresis. [ABSTRACT FROM AUTHOR]

Summary: Patients with immune thrombocytopenic purpura (ITP) often receive corticosteroids as a first‐line treatment strategy. The ability to predict the therapeutic response to corticosteroids before initiating treatment would reduce the risk of adverse events, but biomarkers of this parameter have not yet been established. Here, in a single‐centre, retrospective, cohort study of 127 ITP patients who received corticosteroids as first‐line treatment, we compared several characteristics and test results between those patients with a favourable response to corticosteroids (responder cohort, n = 68) and those with a poor response to corticosteroids (non‐responder cohort, n = 59) to identify potential biomarkers that were predictive of corticosteroid response. We extracted six factors as indicative of poor response to corticosteroid therapy for ITP: old age (≥81 years) (odds ratio [OR], 2.44; p = 0.02); low platelet count (<9 × 109/L) (OR, 2.25; p = 0.02); high level of platelet‐associated IgG (≥445 ng/107cells) (OR, 3.95; p < 0.01), high platelet distribution width (≥ 14.0 g/dL) (OR, 2.00; p = 0.03), high lymphocyte‐to‐monocyte ratio (≥ 3.52) (OR, 1.40, p = 0.04), and low megakaryocyte count in bone marrow (< 85.5/μl) (OR, 1.72; p = 0.04). Thus, our present data support the fact that these six factors are useful biomarkers for predicting corticosteroid response in patients with ITP. [ABSTRACT FROM AUTHOR]

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

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

• All assessable patients with donor HLA-homo to patient HLA-hetero pairs among 5017 single CBT pairs were engrafted neutrophil (38 pairs) and platelets (30 pairs) and revealed a tendency of high incidence of acute GVHD. • Ethnicity-specific conserved extended HLA haplotypes (CEHs) were invariably shared with the same donor HP in 35 pairs. • These findings imply the possibility that HLA-homo iPSC transplantation provides favorable engraftment and accordingly imply the merit of banking iPSC with homozygous major CEHs. Induced pluripotent stem cells (iPSCs) have been applied to clinical regenerative cell therapy. Recently, an iPSC banking system to collect HLA haplotype (HP) homozygous (homo) cells for iPSC transplantation in allogeneic settings was proposed, and tissue transplantation generated from iPSC through banking has just began. We analyzed 5017 single cord blood transplantation (CBT) pairs with HLA-A, -B, -C, -DRB1 allele typing data and found 39 donor HLA homo donor to patient HLA heterozygous (hetero) pairs. Of note, all 39 HLA homo to hetero pairs engrafted neutrophils, except 1 early death pair, and all 30 assessable pairs engrafted platelets. Acute graft-versus-host disease (GVHD) grades II to IV and grades III to IV occurred in 17 and 3 of 38 assessable pairs, respectively. Competing risk regression analysis revealed a favorable risk of neutrophil engraftment and higher risk of acute GVHD compared with HLA-matched CBTs. Thirty-seven of 39 homo to hetero pairs had conserved extended HLA HPs (HP-1, n = 18; HP-2, n = 8; HP-3, n = 7; HP-4, n = 4; HP-5, n = 1) that were ethnicity-specific, and at least 1 of 2 patient HLA-A, -B, -C, and -DRB1 alleles in each locus were invariably shared with the same donor HP in 35 pairs. These findings confirmed our preliminary results with 6 HLA homo CBTs, and a trend of high incidence of acute GVHD was newly observed. Importantly, they imply the possibility that HLA-homo iPSC transplantation provides favorable engraftment and accordingly imply the merit of banking iPSC with homozygous major conserved extended HLA HPs. [ABSTRACT FROM AUTHOR]

Highlights • Microscopic examinations were performed separately by two morphologists. • Interobserver concordance of the percentage of blasts (<5% or ≥5%, ≤2% or >2–<5%) was found. • Interobserver concordance of dysplastic lineages was found. • Interobserver concordance of the diagnosis (MDS or non-MDS) was found. Abstract The diagnosis of myelodysplastic syndromes (MDS) is based on morphology and cytogenetics. However, limited information is currently available on the interobserver concordance of the assessment of dysplastic lineages (<10% or ≥10% in bone marrow (BM)). The revised International Prognostic Scoring System (IPSS-R) described a new threshold (2%) for BM blasts. However, the interobserver concordance of the categories (0–≤2% and >2–<5%) has limited data. The purpose of the present study was to investigate the assessment of dysplastic lineages and IPSS-R reproducibility. Our study was divided into two Steps. In each Step, the microscopic examinations were performed separately by two morphologists. Regarding the category of BM blasts ≤2% and >2–<5%, interobserver agreement was more than 'moderate' in all pairs (kappa test: 0.43–0.90). Regarding dysgranulopoiesis (dysG) and dyserythropoiesis (dysE) in BM, interobserver agreement was more than 'moderate' in all pairs (kappa test, dysG: 0.45–0.96, dysE: 0.45–0.81). Regarding the category of dysmegakaryopoiesis (dysMgk) in BM, interobserver agreement was more than moderate in 4 out of 5 pairs (kappa test: 0.58–1.00), and was fair for one pair (kappa test: 0.37). We consider that high interobserver concordance may be possible for the BM blast cell count (≤2% or >2–<5%) and dysplasia (<10% or ≥10%) of each lineage. [ABSTRACT FROM AUTHOR]

The risk of complication of polycythemia vera (PV) and essential thrombocythemia (ET) by thrombosis in Japanese patients is clearly lower than in western populations, suggesting that genetic background such as race may influence the clinical features. This study aimed to clarify the relationship between genetic mutations and haplotypes and clinical features in Japanese patients with PV and ET. Clinical features were assessed prospectively among 74 PV and 303 ET patients. There were no clinical differences, including JAK2V617F allele burden, between PV patients harboring the various genetic mutations. However, CALR mutation-positive ET patients had a significantly lower WBC count, Hb value, Ht value, and neutrophil alkaline phosphatase score (NAP), and significantly more platelets, relative to JAK2V617F -positive ET patients and ET patients with no mutations. Compared to normal controls, the frequency of the JAK2 46/1 haplotype was significantly higher among patients with JAK2V617F , JAK2Ex12del , or MPL mutations, whereas no significant difference was found among CALR mutation-positive patients. CALR mutation-positive patients had a lower incidence of thrombosis relative to JAK2V617F- positive patients. Our findings suggest that JAK2V617F -positive ET patients and CALR mutation-positive patients have different mechanisms of occurrence and clinical features of ET, suggesting the potential need for therapy stratification in the future. [ABSTRACT FROM AUTHOR]

Fusarium spp. cause a broad spectrum of infection and are relatively resistant to most antifungal agents, leading to unfavorable prognosis, especially in immunocompromised patients. Several reports have shown synergism among amphotericin B, voriconazole (VRC), terbinafine (TRB), and other antifungal agents in vitro, but the most efficacious combination remains to be elucidated. We report the first case of disseminated Fusarium solani infection successfully treated by combination therapy of VRC and TRB accompanied by surgical resection of endocardial lesions. We also review 15 case reports of combination antifungal therapy for fusariosis and 6 case reports of Fusarium endocarditis. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome ( MDS) is a clonal disorder arising from an alteration in multipotent stem cells, which lose the ability of normal proliferation and differentiation. Disease progression occurs in approximately 30% MDS cases. Specific chromosomal alterations seem responsible for each step in the evolution of acute myeloid leukemia ( AML). Multiple genetic aberrations occur during the clonal evolution of MDS; however, few studies report the presence of the Philadelphia (Ph) chromosome. We report a rare case of Ph-positive AML, which evolved during the course of low-risk MDS. The patient, a 76-year-old man with mild leukocytopenia, was diagnosed with MDS, refractory neutropenia ( RN). After 1.5 yr, his peripheral blood and bone marrow were suddenly occupied by immature basophils and myeloblasts, indicating the onset of AML. A bone marrow smear showed multilineage dysplasia, consistent with MDS evolution. Chromosomal analysis showed an additional t(9;22)(q34;q11) translocation. Because progression occurred concurrently with emergence of the Ph chromosome, we diagnosed this case as Ph-positive AML with basophilia arising from the clonal evolution of MDS. The patient was initially treated with nilotinib. A hematological response was soon achieved with disappearance of the Ph chromosome in the bone marrow. Emergence of Ph-positive AML in the course of low-risk MDS has rarely been reported. We report this case as a rare clinical course of MDS. [ABSTRACT FROM AUTHOR]