Clinical significance of the lymphocyte-to-monocyte ratio in multiple myeloma patients with negative minimal residual disease: a single-center retrospective analysis.

Minimal residual disease (MRD) is a surrogate marker for survival in multiple myeloma (MM), while the lymphocyte-to-monocyte ratio (LMR) is a prognostic factor associated with the patients' immunological status. We retrospectively evaluated the clinical impact of MRD negativity and LMR. MRD was analyzed by multicolor flowcytometry (threshold, 1 × 10-5). Fifty-eight patients (median age 70 years) who achieved complete response were included in this study. Twenty-two patients received autologous stem cell transplantation, 14 received daratumumab-based chemotherapy, and 22 received another treatment. Forty-one (70.7%) patients achieved MRD negativity. Over the median follow-up time of 15.1 months, PFS in MRD-negative patients was significantly longer than in MRD-positive patients (P = 0.020). In addition, a high LMR at MRD assessment was associated with MRD negativity (P = 0.019) and long PFS (P = 0.009). Finally, neither MRD negativity nor high LMR at MRD assessment was associated with significantly shorter PFS compared with MRD positivity or low LMR (P = 0.002). In conclusion, high LMR was associated with MRD negativity and can be used as a predictor of long PFS. Change of treatment strategy might be essential for patients with MRD positivity and high LMR at MRD assessment due to their short PFS.

[Utility of core-needle biopsy as a primary diagnostic method for detecting aggressive B-cell lymphoma in the intensive care unit].

A 68-year-old male presented with appetite loss and abdominal distention. The whole-body computed tomography scan revealed an ileocecal mass with a large amount of ascites, which was consistent with malignant lymphoma. Due to the worsening of his general condition following admission, he was intubated and admitted to the intensive care unit (ICU). In the ICU, we performed a core-needle biopsy (CNB) on the left peritoneal mass, the findings of which showed a pathological diffuse infiltration of CD20+ middle-sized lymphoid cells. After chemotherapy was initiated, the patient showed complete response, suggesting that CNB can be performed immediately and safely even on a critically ill patient.

Elevated eosinophil level predicted long time to next treatment in relapsed or refractory myeloma patients treated with lenalidomide.

Lenalidomide is an immunomodulatory drug that is administered commonly in patients with relapsed or refractory multiple myeloma (RRMM). Eosinophils have immunological functions, for instance, in allergic diseases and asthma. The purpose of this study was to investigate the clinical significance of elevated eosinophil levels in patients with RRMM treated with lenalidomide. A total of 59 patients were included. Elevated eosinophil level was defined as an increase in the eosinophil count of ≥250/µL from the eosinophil count on day 1 during the first cycle. The percentage of patients with elevated eosinophil levels was 22.0%. The overall response ratio in the elevated eosinophil group and nonelevated eosinophil group was 84.6% and 63.0% (P = .189), respectively. The median time to next treatment (TTNT) in the elevated eosinophil group was significantly longer than that in the nonelevated group (40.3 months vs 8.4 months; P = .017). Additionally, TTNT in the elevated eosinophil group with partial response (PR) or better was significantly longer than that in the nonelevated eosinophil group with PR or better (40.3 months vs 11.9 months; P = .021). We concluded that elevated eosinophil levels were frequently observed and might predict a longer TTNT in patients with RRMM treated with lenalidomide.

Successful allogeneic peripheral blood stem cell transplantation for an aggressive variant of T-cell large granular-lymphocyte leukemia: A case report.

The aggressive variant of large granular lymphocyte (LGL) leukemia is very rare and the prognosis of this disease is poor. A 47-year-old woman with progressive pancytopenia and severe liver damage visited our institute. Upon hospitalization, about 30% LGL was detected in her peripheral blood and bone marrow samples. Flow cytometry was conducted to analyze lymphocytes in the bone marrow, which revealed the presence of CD3 and T-cell receptor (TCR) α/ß and absence of CD4, CD8, CD16, CD56, CD22, CD79a, and terminal deoxynucleotidyl transferase (TdT). Southern blotting was performed, which revealed the presence of rearrangement of TCR-Cß1 and Jγ. We made a diagnosis of the aggressive variant of T-LGL leukemia, and performed myeloablative allogeneic peripheral stem cell transplantation (allo-HSCT) from an HLA-matched sibling for primary refractory disease of CHOP and hyper CVAD therapy. She is alive in remission with donor-derived T-LGL lymphocytosis in peripheral blood for 7 years after allo-HSCT. Overall, Allo-HSCT could be active against the aggressive variant of LGL leukemia and induce graft-versus-leukemia effect.

Released washed platelet concentrates are effective and safe in patients with a history of transfusion reactions.

BACKGROUND: Plasma removal by washing is an effective approach to prevent transfusion reactions by platelet concentrates (PCs). Recently, washed PCs were released by the Japanese Red Cross Society (JRCS). MATERIALS AND METHODS: This retrospective multicenter study evaluated the efficacy and safety of released washed PCs (RWPCs) between September 2016 and January 2017 in Japan. The RWPCs were prepared by washing leukoreduced apheresis PCs with the platelet additive solution, BRS-A, using automated cell processors. RESULTS: Clinical data were obtained from 91 patients and 1210 RWPC transfusions at 50 institutions. The median number of RWPC transfusions per patient was 8 (range, 1-91). RWPCs were used in 94.5% of the patients with a history of recurrent or severe transfusion reactions for preventing such reactions. Responses of RWPCs were evaluated as complete response (91.6%), partial response (8.2%), no-change (0.2%), and progression (0%) and overall response was equal across subgroups divided by patients' profiles. The median corrected count increment (CCI) at 1 and 24 h post-transfusion were 13.5 (range, 1.9-35.4) × 109/L and 3.5 (range, -13 to 53.6) × 109/L, respectively, and median CCI at 24 h was 5.5 (range, -13 to 53.6) × 109/L in patients without risk factors associated with platelet transfusion refractoriness. Transfusion reactions to RWPCs were observed in only nine transfusions (0.7%), all of which were mild allergic reactions. CONCLUSION: This study demonstrated that RWPCs were effective and safe in patients with a history of transfusion reactions. Further prospective studies on efficacy together with cost-benefit analysis in RWPCs are needed.

[Reduced-intensity umbilical cord blood transplantation for adult patients with fulminant aplastic anemia].

Allogeneic hematopoietic stem cell transplantation is recommended as a curative treatment option for fulminant aplastic anemia with no neutrophil despite the administration of granulocyte-colony stimulating factor. In the absence of an HLA-matched donor, unrelated cord blood transplantation (UCBT) is a treatment option that can be performed quickly. However, the optimal conditioning regimen of UCBT is yet to be established. We report two cases of fulminant aplastic anemia in adult patients who received UCBT. The first patient was a 52-year-old woman and the second was a 26-year-old man, both of whom received a conditioning regimen of total body irradiation (TBI; 2-4 Gy), fludarabine (Flu; 120 mg/kg), and cyclophosphamide (CY; 100 mg/kg) before UCBT. Short-term methotrexate and tacrolimus were used for prophylaxis of acute graft-versus-host disease (GVHD). Engraftments were achieved on days 26 and 19, and they exhibited complete donor chimerism by days 28 and 34. There was no evidence of acute GVHD, and therefore, the immunosuppressant drugs were discontinued. Reduced-intensity UCBT using a low-dose TBI/Flu/CY conditioning regimen could be an effective treatment option for fulminant aplastic anemia in the absence of a suitable donor.

Clinical significance of granule-containing myeloma cells in patients with newly diagnosed multiple myeloma.

The clinical features and prognostic significance of myeloma cells containing granules remain unclear. The purpose of this retrospective study was to investigate the clinical significance of granule-containing myeloma cells in patients with newly diagnosed multiple myeloma (NDMM). We retrospectively analyzed the records of 122 patients diagnosed with NDMM between January 2007 and December 2013. Granule-containing myeloma cells were defined as myeloma cells that exhibited three or more granules in their cytoplasm by May-Giemsa staining. The patients were classified into two groups, the granule-containing myeloma (GM) and nongranule-containing myeloma (non-GM) groups, depending on the proportion of myeloma cells that contained granules (cut-off value: 10%). There were 25 (20.5%) patients in the GM group. Patients in the GM group displayed significantly higher CD56 and CD49e expression than those in the non-GM group (t-test, P = 0.027 and 0.042). None of the patient characteristics differed significantly between the two groups. There was no significant difference in the chemotherapy profiles of the two groups, and the overall response rates of the two groups were similar. During the median follow-up period of 33.9 months, the overall survival (OS) in the GM group was similar to that in the non-GM group; 4-year OS of the GM and non-GM groups were 78.5% and 51.9%, respectively (P = 0.126). We concluded that cases of NDMM involving granule-containing myeloma cells are not infrequent. Moreover, CD56 and CD49e expression was significantly higher in the presence of myeloma cell populations, and the presence of granules did not affect survival.

A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction.

Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined. Complete molecular response was observed in 75/152 patients (49.3%). In the univariate analysis, Sokal score, median time to major molecular response, ABCG2 421C>A, and regulatory T cells were significantly lower in chronic phase chronic myeloid leukemia patients with complete molecular response than in those without complete molecular response. In the multivariate analysis, duration of imatinib treatment (odds ratio: 1.0287, P=0.0003), time to major molecular response from imatinib therapy (odds ratio: 0.9652, P=0.0020), and ABCG2 421C/C genotype (odds ratio: 0.3953, P=0.0284) were independent predictors of complete molecular response. In contrast, number of natural killer cells, BIM deletion polymorphisms, and plasma trough imatinib concentration were not significantly associated with achieving a complete molecular response. Several predictive markers for achieving complete molecular response were identified in this study. According to our findings, some chronic myeloid leukemia patients treated with imatinib may benefit from a switch to second-generation tyrosine kinase inhibitors (ClinicalTrials.gov, UMIN000004935).

[Draft proposal to estimate true values of serum potassium in samples from patients with myeloproliferative neoplasma].

The pseudohyperkalemia in thrombocytosis is assumed to be due to potassium released from blood cells during blood clotting as reported previously, but its mechanisms remain to be cleared. Although plasma potassium measurements with blood collection tubes containing heparin are performed in many hospitals to avoid pseudohyperkalemia, the burden on patients may come out with further blood sampling by another heparinized tube. Taken together, we investigated laboratory data possibly involved in pseudohyperkalemia in 184 samples from patients with myeloproliferative neoplasma (MPN), and studied estimation capability for true values of serum potassium, driving a correction formula by means of several laboratory data to explain the difference of measured potassium values (K-difference: serum value minus plasma value). Platelet count and mean corpuscular volume (MCV) were adopted as significant variables correlated to K-difference as a result of multiple regression analysis. A correction formula was driven by multiple regression equation with these two variables as follows: y = 0.0006 x 1+0.0004 x 2-0.177 (r= 0.885; x 1, platelet count; x 2, MPV). The correction formula was considered to be useful for estimating the true value of serum potassium in samples from patients with MPN because the corrected serum potassium value correlated highly with plasma potassium value (r = 0.885). These results propose that true values of serum potassium can be estimated by the correction of measured serum potassium values with platelet count and MCV, suggesting that not only quantitative factors but also qualitative factors may be involved in pseudohyperkalemia.

[Fatal septic shock and rhabdomyolysis following transfusion of platelet concentrates contaminated with Streptococcus pneumoniae].

We report on a 58-year-old male diagnosed as having primary myelofibrosis with thrombocytopenia, who died of fatal septic shock and rhabdomyolysis after platelet concentrates (PCs) transfusion. The initial diagnosis of primary myelofibrosis was established by splenomegaly, leukoerythroblastosis and bone marrow fibrosis. PCs were transfused because of thrombocytopenia with marked bleeding tendency. Soon after the PCs transfusion in March 2000, he had attacks of chest pain, back pain and myalgia, then went into shock and died of unknown causes. PCs were suspected as being the cause of death, because Streptococcus pneumoniae was found in the culture of PCs in the WBC-reduction in-line filter and fresh frozen plasma from the same donor preserved in the Japan Red Cross Center. Rhabdomyolysis, neutrophil infiltration and phagocytosed bacteria were found from the autopsy materials, which were identified by DNA analysis as the same species found in the PCs. PCs are kept at room temperature because platelet function is lost in the cold. When PCs are contaminated with bacteria, marked multiplication induces fatal bacteremia. This is a rare report in Japan of fatal septic shock caused by PCs with bacterial contamination. We must pay strict attention to bacterial contamination in blood components.