Masuoka H

Prognostic factors of hemophagocytic syndrome in adults: analysis of 34 cases

Abstract: Hemophagocytic syndrome (HPS) presents with fever, pancytopenia, liver dysfunction and increase in hemophagocytic histiocytes in various organs. Although there are two major classifications of HPS in adults, malignant and reactive histiocytosis, it is often very difficult to distinguish between these disorders. We analyzed the laboratory data of patients with HPS to evaluate prognostic factors. Of 34 patients, 14 survived, and 20 died. The median age of survivors was 29.6 ± 11.5 yr significantly younger than those who died (54.7 ± 17.8 yr). Twenty patients had no obvious underlying disease, the other 13 had hematological malignancies or viral infections. Comparison of laboratory data revealed that nonsurvivors had significantly lower Hb and platelet values on admission. During treatment, worsening of anemia and thrombocytopenia, increase of transaminase and biliary enzymes were similarly more prominent. Risk factors associated with death were: age over 30 yr, presence of disseminated intravascular coagulation, increased ferritin and β2‐microglobulin, anemia accompanied by thrombocytopenia and jaundice. Our data suggests that patients with HPS and any of these risk factors should be treated aggressively with sufficient chemotherapy and supportive care.

Long‐term administration of G‐CSF for aplastic anaemia is closely related to the early evolution of monosomy 7 MDS in adults

There is an increasing incidence of the evolution of myelodysplastic syndrome (MDS) from aplastic anaemia (AA) with immunosuppressive treatment. In paediatric patients G‐CSF is also reported to increase MDS evolution, but this process is not precisely understood in children or in adults. Therefore risk factors of MDS evolution in adults are evaluated here. Of 72 patients, five developed MDS. In 47 patients without cyclosporine (CyA) or antithymocyte globulin (ATG) therapy, only one developed MDS with trisomy 8, 242 months after diagnosis. But of 25 patients treated with either CyA or ATG, four developed monosomy 7 MDS within 3 years. Of these 25 patients, 18 were treated with G‐CSF and the four patients (22.2%) who developed MDS were found in this group. The cumulative dose and the duration of G‐CSF administration were significantly elevated in patients who developed MDS when compared with those who did not, 822.3 ± 185.0 v 205.4 ± 25.5 μg/kg (P < 0.05) and 187.5 ± 52.5 v 72.0 ± 24.6 d (P < 0.002), respectively. However these two values for CyA did not differ significantly. Statistically, treatment with CyA, G‐CSF and combined G‐CSF and CyA were significantly related to MDS evolution. The administration of G‐CSF for more than a year was the most important factor (P = 0.00). These results suggested that a close relationship exists between G‐CSF and subsequent monosomy 7 MDS from AA in adults who receive immunosuppressive therapy. Long‐term administration of G‐CSF should be prohibited in order to prevent MDS evolution.

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).

Combination Chemotherapy with G-CSF, M-CSF and EPO: Successful Treatment for Acute Myelogenous Leukemia without Blood Transfusion at Lower Medical Costs

A 55-year-old Jehova’s Witness was treated for acute myelogenous leukemia (AML) by intensive chemotherapy with enocitabine, 6-mercaptopurine and daunorubicin. G-CSF, M-CSF and EPO were subsequently administered. Even though no blood transfusion was given for religious reasons, complete remission was achieved without serious infection and hemorrhage. The total cost for induction chemotherapy was less expensive than is the case for elderly AML patients. This case indicates that the administration of cytokines might reduce the incidence of infection and the necessity for blood products, which would result in favorable cost effectiveness for the treatment of elderly patients with AML.

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.