Complex karyotype determined using conventional cytogenetic analysis is a poor prognostic factor in patients with multiple myeloma.

High-risk cytogenetic abnormalities (HRCAs) influence the prognosis of multiple myeloma (MM). However, additional cytogenetic aberrations can lead to poor outcomes. This study aimed to clarify whether HRCAs and additional chromosomal abnormalities affect MM prognosis. Patients with newly diagnosed MM who were treated with novel agents were retrospectively evaluated. The primary objective was to assess the difference in progression-free survival (PFS) and overall survival (OS) between patients with/without HRCAs and between patients with/without complex karyotype (CK). The secondary objectives were to identify factors affecting PFS/OS and factors related to CK. HRCAs were defined as del(17p), t(4;14), t(14;16), and gain/amplification(1q) assessed using fluorescence in situ hybridization. CK was defined as ≥3 chromosomal abnormalities on G-banding. Among 110 patients, 40 had HRCAs and 15 had CK. In this study, survival durations between patients with/without HRCAs were similar, while the CK group had significantly poorer PFS/OS than the no-CK group (median PFS: 9 vs. 24 months and median OS: 29 vs. 97 months, respectively), and a poor prognostic impact of CK was maintained in patients with HRCAs. In multivariate analysis, CK was correlated with poor PFS/OS (hazard ratio [HR]: 2.39, 95% confidence interval [95% CI]: 1.22-4.66 and HR: 2.66, 95% CI: 1.10-6.45, respectively). Bone marrow plasma cell (BMPC) ≥60% (odds ratio [OR] = 6.40, 95% CI: 1.50-27.2) and Revised International Staging System III (OR = 7.53, 95% CI: 2.09-27.1) were associated with CK. Our study suggests that CK may contribute to the poor prognosis of MM. Aggressive disease status including high BMPC proliferation could be relevant to CK.

Prognostic value of post-treatment serum soluble interleukin-2 receptor in newly diagnosed diffuse large B-cell lymphoma patients who achieved complete metabolic response following R-CHOP therapy.

Patients with DLBCL achieving complete metabolic response (CMR) after initial treatment with R-CHOP generally have a favourable prognosis; however, there are no established prognostic biomarkers for relapse in these patients. Soluble interleukin-2 receptor (sIL-2R) levels at diagnosis are prognostic factors in patients with DLBCL. However, the significance of post-treatment sIL-2R levels is unclear. To determine the significance of post-treatment serum sIL-2R levels on subsequent relapse and survival, we retrospectively analysed 485 patients with newly diagnosed DLBCL who received R-CHOP treatment and achieved CMR. The cumulative incidence of relapse (CIR) was significantly higher in patients with elevated post-treatment sIL-2R levels than in those with normal sIL-2R levels (five-year CIR; 38.8% vs. 12.8%). The prognostic value remained significant in multivariable analysis (hazard ratio, 2.30; p < 0.001). Five-year progression-free survival (49.0% vs. 83.5%) and overall survival (61.7% vs. 91.6%) rates were lower in patients with elevated post-treatment sIL-2R levels than in those with normal sIL-2R levels (p < 0.001 for both). In patients with newly diagnosed DLBCL who achieved CMR after R-CHOP treatment, the post-treatment serum sIL-2R level was an independent prognostic marker of subsequent relapse and survival.

[Immunohistochemical evaluation of BCL-2 expression in acute myeloid leukemia, myeloid sarcoma, and blastic plasmacytoid dendritic cell neoplasm].

Venetoclax, a selective BCL-2 inhibitor, is prescribed clinically for acute myeloid leukemia (AML) treatment. However, it is unclear if known chromosomal or genetic abnormalities associated with AML also influence BCL-2 expression. Few studies have examined BCL-2 expression in AML-related precursor neoplasms such as primary myeloid sarcoma (MS) and blastic plasmacytoid dendritic cell neoplasm (BPDCN). In this study, we examined BCL-2 expression using immunohistochemistry in 7 patients with AML, who also carried genetic and chromosomal abnormalities typical to AML including t (8;21), t (15;17), FLT3-ITD mutation, and complex karyotype, along with 1 patient with primary MS and 3 patients with BPDCN. As a result, expression of BCL-2 was observed in all patients with AML and 1 patient with primary MS. In the patients with BPDCN, BCL-2 was highly expressed in all regions with evidence of tumor cell infiltration, such as skin, bone marrow, and lymph node. These results could be used as evidence in the support of administering venetoclax to adverse-risk patients with AML, MS, or BPDCN.

A novel mutation causing type 1 Gaucher disease found in a Japanese patient with gastric cancer: A case report.

RATIONALE: Gaucher disease (GD) is an autosomal recessive disorder that leads to multiorgan complications caused by ß-glucocerebrosidase deficiency due to mutations in the ß-glucocerebrosidase-encoding gene (GBA). GD morbidity in Japan is quite rare and clinical phenotype and gene mutation patterns of patients with GD in Japan and Western countries differ considerably. Of Japanese patients with GD, 57% develop types 2 or 3 GD with neurologic manifestations and younger onset, whereas only 6% of patients with GD develop those manifestations in Western countries. Thus, it is relatively difficult to find and diagnose GD in Japan. PATIENT CONCERNS: A 69-year-old Japanese female with mild anemia and thrombocytopenia but without neurologic symptoms was initially referred for gastric cancer. Preoperative F-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showed accumulation in the bone marrow and paraabdominal lymph nodes. Following bone marrow aspiration found, abnormal foamy macrophages in the bone marrow and electron microscopy revealed that the macrophages were filled with tubular-form structures. Adding to these signs suggestive of a lysosomal disease, serum ß-glucocerebrosidase activity test found decreased. Sequencing of the patient's GBA gene revealed a RecNciI recombinant mutation and the novel mutation K157R (c.587A>G). DIAGNOSES: On the basis of these findings and clinical manifestations, the final diagnosis of type 1 GD was made. INTERVENTIONS: Enzyme replacement therapy (ERT) with velaglucerase α was started after the diagnosis of type 1 GD. OUTCOMES: The patient's ß-glucocerebrosidase activity as well as hemoglobin and platelet levels were restored by ERT without any side effects. Bone marrow aspirations 10 months after the start of the treatment with velaglucerase α showed reduction of Gaucher cells in bone marrow to 2% from 4% of total cellularity. LESSONS: This is the first report of F-FDG PET/CT application providing a clue for GD diagnosis. A novel mutation in GBA is described, which implies a potential pool of patients with GD with this mutation in Japan.

[Significance of monitoring cerebrospinal fluid leukocyte counts in managing central nervous system disease of acute myeloid leukemia in patients presenting with intracerebral hemorrhage upon initial examination].

A 17-year-old woman was urgently transported to our hospital due to consciousness disturbance. A blood examination revealed intracerebral hemorrhage, WBC 233,800/l, blasts 93%, and disseminated intravascular coagulation. The results of bone-marrow aspiration indicated acute myeloid leukemia (M2 in FAB classification) with t (7;11) (p15;p15) and the resulting chimeric gene NUP98-HOXA9 and with FLT3-ITD. Following hematoma evacuation, induction therapy was initiated and the leukocytes in the cerebrospinal fluid observed in the spinal drainage were monitored. Because they increased on days 5 and 9 after the completion of induction therapy, intrathecal chemotherapy (IT) was performed; this finally contributed to controlling AML in the central nervous system (CNS), together with the restoration of normal hematopoiesis. Subsequently, after complete molecular remission with consolidation therapies containing high-dose cytarabine, a bone-marrow transplantation with a myeloablative regimen was conducted from a 1-allele mismatched sibling donor. Finally, the patient was discharged without major sequela on day 228 after the first visit. The management of CNS disease in AML with intracerebral hemorrhage remains unclear. Our case suggests that IT at the appropriate time based on the monitored number of cerebrospinal fluid leukocytes could be useful in controlling AML in the CNS after intracerebral hemorrhage.