[Multiple extramedullary plasmacytomas responding to a reduced dose of carfilzomib following drug-induced thrombotic microangiopathy].

Herein, we report the findings of a 79-year-old male patient who presented with multiple extramedullary plasmacytomas following a relapse of primary plasma cell leukemia. He developed thrombotic microangiopathy (TMA) while receiving carfilzomib, lenalidomide, and dexamethasone (KLd) therapy. He was diagnosed with plasma cell leukemia 3 years ago; he demonstrated a very good partial response (VGPR) after undergoing two regimens, including either bortezomib or lenalidomide, and he had been followed up without any other treatment due to complications of infection. Following relapse, KLd was initiated. On day 7 of KLd, TMA developed; therefore, the treatment was discontinued. The TMA improved only with the discontinuation of KLd. A reduced dose of KLd was readministered; the TMA did not relapse. He demonstrated VGPR after three courses of reduced-KLd; he has since remained in remission through ten courses. Therefore, carfilzomib therapy may be useful in relapsing and refractory cases. Drug-induced TMA has been reported to be caused by either immune-mediated or dose-dependent toxicity mechanisms. In patients who develop dose-dependent TMA with carfilzomib, dose reduction could be considered in cases showing an effective response to the treatment.

Myeloid leukemoid reaction after initial azacitidine therapy for chronic myelomonocytic leukemia.

The development of myeloid leukocytosis in leukemia patients during antileukemic treatment requires a differential diagnosis between myeloid leukemoid reaction and leukemia progression. We herein report the case of an 80-year-old Japanese man with chronic myelomonocytic leukemia (CMML) who developed marked myeloid leukocytosis (36.3 × 109/L) with 32.5% monocytes and 48% neutrophils about 4 weeks after the initial 5-azacitidine (AZA) treatment. The leukocytosis was unlikely to be attributed to infection and adverse drug reaction. As it resolved in a few days without any interventions, the transient myeloid leukocytosis was confirmed to be a myeloid leukemoid reaction. After four cycles of AZA treatment, leukemic blasts in the bone marrow decreased and the patient became transfusion-independent. Interestingly, levels of serum G-CSF showed a similar trend to the myeloid leukocytosis, while those of serum GM-CSF and IL-17 were undetectable throughout the clinical course, suggesting that a differentiation response to AZA treatment might lead to the myeloid leukemoid reaction. Our case implies that a marked but transient myeloid leukemoid reaction mimicking CMML progression can develop during AZA treatment, which requires careful clinical monitoring and differential diagnosis.

Clinical features of adult acute leukemia with 11q23 abnormalities in Japan: a co-operative multicenter study.

To clarify the clinical features of adult patients with acute leukemia (AL) with 11q23 abnormalities, we performed a retrospective analysis of data from 58 adult Japanese patients: 51 with acute myeloid leukemia (AML), and 7 with acute lymphoblastic leukemia (ALL). The incidences according to fusion partners in AML were: t(9;11), 31.3%; t(11;19), 27.4%; t(6;11), 21.5%. The incidence of patients with t(11;19) was higher than those in the US and Europe, and the incidence of t(4;11) was lower than that in childhood. The results indicated the poor prognosis of AML with 11q23 abnormalities regardless of the fusion partners. AML patients with 11q23 aged <60 years in the first CR who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) showed a more favorable outcome than those treated without allo-HSCT, although the differences were not statistically significant (P = 0.322 for DFS, P = 0.138 for OS). This result suggests that treatment strategies including allo-HSCT may be considered in the first CR in cases of AML with 11q23 abnormalities. However, further studies involving a large number of cases are required to assess the effect of allo-HSCT on adult AL with 11q23 abnormalities.

Clinical significance of phenotypic features of blasts in patients with myelodysplastic syndrome.

Knowledge of the blast phenotype in myelodysplastic syndrome (MDS) would be valuable, as in other malignancies, but remains sparse. This is mainly because MDS blasts are a minor population in clinical samples, making analysis difficult. Thus, for this blast phenotype study, we prepared blast-rich specimens (using a new density centrifugation reagent for harvesting blasts) from blood and marrow samples of 95 patients with various MDS subtypes and 21 patients with acute leukemia transformed from MDS (AL-MDS). Flow cytometry revealed that a high proportion of the enriched blast cells (EBCs) from almost all patients showed an immunophenotype of committed myeloid precursors (CD34(+)CD38(+)HLA-DR(+)CD13(+)CD33(+)), regardless of the disease subtype. The cytochemical reaction for myeloperoxidase was negative in 58% of the cases. Thus, the EBC phenotype is more immature in MDS than in de novo acute myeloid leukemia. MDS EBCs often coexpressed stem cell antigens and late-stage myeloid antigens asynchronously, but rarely expressed T- and B-lymphoid cell-specific antigens. Markers for myeloid cell maturation (CD10 and CD15) were more prevalent on EBCs from low-risk MDS (refractory anemia [RA] and RA with ringed sideroblasts), whereas markers for myeloid cell immaturity (CD7 and CD117) were more prevalent on EBCs from high-risk MDS (chronic myelomonocytic leukemia, RA with excess blasts [RAEB], and RAEB in transformation) and AL-MDS. A shift to a more immature phenotype of EBCs, accompanying disease progression, was also documented by sequential phenotyping of the same patients. Further, CD7 positivity of EBCs was an independent variable for a poor prognosis in MDS. These data represent new, valuable information regarding MDS.