Atsushi Isoda

Chronic inflammatory demyelinating polyneuropathy accompanied by chronic myelomonocytic leukemia: possible pathogenesis of autoimmunity in myelodysplastic syndrome

Paraneoplastic neuropathies have rarely been reported in patients with hematological malignancies. We report herein the case of a 65-year-old Japanese woman with chronic myelomonocytic leukemia (CMML) accompanying chronic inflammatory demyelinating polyneuropathy (CIDP). She had been diagnosed with refractory anemia and subsequently developed CMML with cytogenetic abnormalities including t(3;8)(q26;q24). While regenerating bone marrow following induction chemotherapy, she complained of numbness in the lower legs and then became unable to walk. Clinical and electrophysiological features were consistent with CIDP. Intravenous immunoglobulin treatment was insufficient, although corticosteroids reduced neurological symptoms. This case suggests CIDP as one of the autoimmune phenomena associated with myelodysplastic syndrome and immunosuppressive treatment represents an effective therapy.

Trends of survival in patients with multiple myeloma in Japan: a multicenter retrospective collaborative study of the Japanese Society of Myeloma.

Trends of survival in patients with multiple myeloma in Japan: a multicenter retrospective collaborative study of the Japanese Society of Myeloma

The naive T‐lymphocyte compartment is well preserved in patients with chronic myelogenous leukaemia in chronic phase

Summary. In chronic myelogenous leukaemia (CML), clonal change occurs in all myeloid and B‐cell lineages, but very rarely T‐cell lineages. A detailed three‐colour cytometric analysis of peripheral lymphocytes was performed in 22 patients with chronic‐phase CML (CP‐CML). CD45 gating analysis was used to discriminate between lymphocytes and basophils. The peripheral lymphocyte pool was comprised of a significant proportion of naive CD4 cells, defined by a CD4+45RA+ phenotype [47·0 ± 19·6% (mean ± SD) of the total CD4+ cells], and naive CD8 cells, defined by a CD8+CD45RA+CD28+ phenotype (35·1 ± 19·7% of total CD8+ cells), even in patients with long disease duration. The percentage of CD8 naive T cells showed inverse correlation with age, whereas no correlation was observed with disease duration. Possible explanations for the preservation of naive lymphocytes include (1) that the naive T cells differentiated from co‐existing normal stem cells or (2) that long‐lived naive T cells persisted from the CML onset and expanded peripherally (thymus independent). Either mechanism or a combination of both mechanisms might contribute to maintaining the naive compartment size.

TCR Vβ repertoire analysis in CD56+ CD16dim/− T-cell large granular lymphocyte leukaemia: association with CD4 single and CD4/CD8 double positive phenotypes

Summary.  We report 10 patients with T‐cell large granular lymphocyte (LGL) leukaemia: four patients had CD16+ CD56− LGL lymphocytes (typical for LGL leukaemia), and six patients had CD56+ CD16dim/− LGL lymphocytes (atypical). Among the CD56+ CD16dim/− patients, LGL lymphocytes were CD4+ CD8− in one patient, CD4/CD8 double positive (DP) in three, and CD4− CD8+ in two. The CD4+ CD8dim DP cells expressed a CD8αα homodimer. T‐cell receptor (TCR) Vβ complementarity‐determining region 3 (CDR3) size distribution analysis and direct sequencing identified at least 1 in‐frame clonal TCR Vβ transcript in each patient; three patients had two or three different clonal sequences. To determine whether these transcripts were translated into cell surface TCR, we performed flow cytometric analysis using Vβ monoclonal antibodies (mAbs). A single Vβ protein was identified in patients, even those with multiple in‐frame transcripts. Previous and present results suggest that CD56+ CD16dim/− LGL leukaemia is more common than previously thought, and is associated with unusual phenotypes. When assessed using only molecular techniques, the monoclonal status of this disease may be misinterpreted as oligoclonal; thus, flow cytometric analysis using Vβ mAb is quite useful. Because mAbs do not cover the entire Vβ repertoire, assessing clonality using a combination of molecular methods and mAbs is preferable.

A new staging system to predict prognosis of patients with multiple myeloma in an era of novel therapeutic agents

Various prognostic markers for multiple myeloma (MM) have been identified, and stratification using these markers is considered important to optimize treatment strategies. The international staging system (ISS) is now a widely accepted prognostic staging system for MM patients; however, its validity is controversial in the era of new therapeutic regimens, since ISS had been established before introduction of new agents. We retrospectively reviewed prognostic factors in order to seek out an alternative staging system more suitably applied to MM patients treated with novel agents. We analyzed 178 newly diagnosed MM patients who received either conventional chemotherapy without novel agents (CT; n = 79) or chemotherapy with novel agents (NT; n = 99). Although median overall survival (OS) of patients treated with CT is significantly different depending on stages of ISS, ISS had no effect on OS among patients treated with NT. Meanwhile, we identified hemoglobin (Hb) and plasmacytoma as independent risk factors for OS in patients who received NT. Using these two parameters, we stratified NT patients into three stages; stage 1 (Hb≥10 g/dL and absence of plasmacytoma), stage 2 (not stage 1 or 3), and stage 3 (Hb <10 g/dL and presence of plasmacytoma). We found that there were significant differences in median OS among the three stages (8.13, 5.95, and 2.45 yr for stages 1, 2, and 3, respectively). This preliminary study suggests that this alternative staging system based on Hb and plasmacytoma is a simple and useful way to predict prognosis of MM patients in the novel agent era.

Expression of CD55 and CD59 on peripheral blood cells in patients with lymphoproliferative disease of granular lymphocytes.

Lymphoproliferative disease of granular lymphocytes (LDGL) is a disorder characterized by the clonal expansion of granular lymphocytes. It has recently been shown that the clonal expansion of granular lymphocytes occurs in patients with paroxysmal nocturnal hemoglobinuria (PNH) in a subclinical fashion. To test the possibility that LDGL patients share a PNH phenotype, we obtained peripheral blood cells from 20 patients with LDGL and examined the expression of the glycosylphosphatidyl inositol (GPI)‐anchored proteins, CD55 and CD59. Compared with normal controls, however, a defective expression of CD55/59 was not observed on either granulocytes or erythrocytes from LDGL patients. An unexpected finding was the significantly lower CD55/59 expression on granular lymphocytes from patients with CD16+CD56− phenotype LDGL than from patients with CD16+CD56+ phenotype LDGL, or natural killer (NK) and NK/T lymphocytes from healthy individuals. The positive correlation between the expression of CD56 and CD55/59 might have some relevance to the functional properties of the CD56+ subset of large granular lymphocytes.

Intra-patient dose escalation of panobinostat in patients with relapsed/refractory multiple myeloma

To the Editor,Panobinostat (LBH589, FARYDAK®) is a nonselective histone deacetylase inhibitor that has shown synergistic anti-myeloma activity in combination with bortezomib [1]. In a pivotal phase...

Retrospective analysis of prognostic factors for Waldenstrӧm macroglobulinemia: a multicenter cooperative study in Japan.

Although population-based cancer registries have reported lower incidence of Waldenstrӧm macroglobulinemia (WM) in East Asia than in Western countries, previous retrospective analyses have found the clinical features of WM to be similar in these two populations. To clarify the characteristics of Japanese WM patients, we retrospectively analyzed clinical and laboratory characteristics, treatments, outcomes, and prognostic factors in 93 patients with WM. Based on the Second International Workshop on WM (IWWM-2) criteria, symptomatic WM was found in 73 (78.5%) and asymptomatic WM in 20 (21.5%) of cases examined. The median overall survival (OS) was similar to that in reports from Western countries. Patients receiving treatment regimens including rituximab exhibited significantly better survival than those not given rituximab. Although prognostic factors for WM in Western countries may not apply to Japanese patients, our finding that newly diagnosed WM patients with pleural effusion have a poorer prognosis suggests that this may be a novel predictor of adverse prognosis in symptomatic WM.