The autosomal dominant macrothrombocytopenia with leukocyte inclusions, May-Hegglin anomaly (MHA), Sebastian syndrome (SBS), and Fechtner syndrome (FTNS), are rare platelet disorders characterized by a triad of giant platelets, thrombocytopenia, and characteristic Döhle body-like leukocyte inclusions. The locus for these disorders was previously mapped on chromosome 22q12.3-q13.2 and the disease gene was recently identified as MYH9, the gene encoding the nonmuscle myosin heavy chain-A. To elucidate the spectrum of MYH9 mutations responsible for the disorders and to investigate genotypephenotype correlation, we examined MYH9 mutations in an additional 11 families and 3 sporadic patients with the disorders from Japan, Korea, and China. All 14 patients had heterozygous MYH9 mutations, including three known mutations and six novel mutations (three missense and three deletion mutations). Two cases had Alport manifestations including deafness, nephritis, and cataracts and had R1165C and E1841K mutations, respectively. However, taken together with three previous reports, including ours, the data do not show clear phenotype-genotype relationships. Thus, MHA, SBS, and FTNS appear to represent a class of allelic disorders with variable phenotypic diversity.

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Biphenotypic acute leukemia (BAL) is a rare yet defined type of acute leukemia. We investigated the incidence, clinicopathologic characteristics, and clinical outcomes of BAL in Korean adults. The present study retrospectively analyzed clinicopathological and clinical data from 43 adult patients with BAL, defined using the EGIL scoring system, from 11 Korean institutes. The incidence of BAL was 2.1% among acute leukemias; 2.3% in male and 1.9% in female. Median age of 43 BAL patients, 25 males and 18 females, was 38 years (range, 16–74). The immunophenotype was myeloid/B-lymphoid (M+B) in 31 (72.1%), myeloid/T-lymphoid (M+T) in 10 (23.3%), and B/T-lymphoid (B+T) and myeloid/B/T-lymphoid (M+B+T) in one (2.3%) each. 37 patients had the results of cytogenetic analyses and Ph chromosome (n=14, 37.8%) was the single most common abnormal finding. Intensive induction chemotherapy was given in 36 of 43 patients: AML-type in 13 (36.1%), ALL-type in 8 (22.2%), and combined type in 15 (41.7%). Complete remission (CR) was induced in 29 patients (80.6%). The CR rate was significantly lower in M+T (5 of 9, 55.6%) than M+B (22 of 25, 88.0%) (P=0.039). Other unfavorable factors for CR were absence of CD19 (P=0.029) or CD20 (P=0.046), and presence of CD2 (P=0.040). The CR rates were not significantly different according to cytogenetic finding or type of induction chemotherapy. After median follow-up duration of 712 days among surviving patients, 11 patients relapsed with median relapse-free survival (RFS) of 3.08 years and 4-y RFS of 38.3% and 18 patients died with median overall survival (OS) of 2.49 years and 4-y OS of 30.1%. Multivariate analysis showed that high leukocyte counts (≥ 30,000/μl) at diagnosis (OR, 5.922; 95% CI, 1.379–25.429; P=0.017) was an independent unfavorable prognostic factor for RFS, and high leukocyte counts at diagnosis (OR, 9.348; 95% CI, 3.014–28.993; P<0.001) and M+T phenotype (OR, 3.259; 95% CI, 1.136–9.344; P=0.028) were independent unfavorable prognostic factors for OS. In summary, BAL was found in 2.1% of adult acute leukemias and M+T phenotype showed significantly poorer response to induction chemotherapy and inferior overall survival compared to M+B phenotype.

Monoclonal immunoglobulin, as a marker for monoclonal gammopathy, is evaluated by protein electrophoresis (PEP) and immunofixation electrophoresis (IFE). However, PEP and IFE are not satisfactory in sensitivity, objectivity, and facility. Recently, a highly sensitive, automated immunoassay for measurement of free light chain (FLC) concentrations in serum and urine has been developed for the identification and monitoring of patients with monoclonal gammopathy. To explore the clinical usefulness of measurement of FLC concentrations, we measured the kappa and lambda FLC concentrations and calculated the kappa/lambda FLC ratios for three groups [multiple myeloma (MM), other diseases, and control] and compared the results of the FLC assay with the results of PEP or IFE. The concentrations of serum kappa and lambda FLCs and the kappa/lambda FLC ratios for the MM group and non-MM groups were distinct. In the MM group, some sera and urine samples had no evidence of M protein on PEP and IFE, but FLC assay showed abnormal concentrations of FLCs and abnormal kappa/lambda FLC ratios in most cases. As compared with the PEP, the kappa/lambda FLC ratio revealed higher sensitivity in all diagnostic ranges with different cutoff values. Particularly, when the cutoff value 2.0 for kappa/lambda FLC ratio was used, specificity and positive predictive value were largely improved than when the cutoff values 1.2 and 1.5 were used. These findings indicated that FLC assay enables to detect myeloma patients with very low M protein due to early stage or after therapy and to distinguish patients with monoclonal increase of FLC from patients with polyclonal increase of FLC due to other conditions, particularly using kappa/lambda FLC ratio 0.3-2.0 as a diagnostic range. Despite some technical limitations of the assay, the incorporation of kappa/lambda FLC ratios with FLC concentrations is useful in the detection of M protein, particularly with negative serum or urine IFE results, and differentiation of monoclonal gammopathies from patients with polyclonal increase in FLC due to other conditions.

The frequency of thromboembolic events (TE) in Caucasian patients with multiple myeloma (MM) receiving thalidomide as the initial treatment has been reported to be 10~58% without prophylactic anticoagulation. Korean MM patients treated with thalidomide were studied to determine the frequency of TE and associated risk factors. A retrospective medical record review of the Korean MM registry from 25 centers in Korea between 2003 and 2007 was performed. We assessed the incidence of arterial and venous TE and the associated clinical parameters. Three hundred and sixty MM patients (median age 61 years, range 32-88 years) received thalidomide treatment. Fourteen patients (3.9%) developed TE: 12 had venous and two had arterial locations. The sites for the venous TE included lungs (seven), lower extremities (four), upper extremities (one), and neck (one). Arterial TE developed in cerebral and peripheral arteries each. No single clinical parameter such as prerequisite for the metabolic syndrome, disease status, and treatment regimen were predictive for the development of TE. The frequency of TE in patients who received thalidomide as initial therapy (7/155) was not different from those who received thalidomide for progressive or relapsed disease (7/205, p = 0.592). The frequency of TE during thalidomide treatment in Korean patients with MM was low. No significant clinical factor was found to be a risk factor. The subgroup requiring thromboprophylaxis among the Korean patients with MM, receiving thalidomide, needs to be clarified.