Causes of macrocytic anemia among 628 patients: mean corpuscular volumes of 114 and 130 fL as critical markers for categorization.

There have been no studies on the distribution of causes of macrocytic anemia with respect to mean corpuscular volume (MCV) cutoff values. We retrospectively investigated the causes of macrocytic anemia (MCV ≥100 fL) among 628 patients who visited the outpatient hematology clinic in Tohoku University Hospital. To ensure data validity, we also analyzed data from 307 patients in eight other hospitals in the Tohoku district. The leading causes of macrocytic anemia (number of patients, %) were myelodysplastic syndromes (121, 19.3 %), suspected bone marrow failure syndromes (BMF; 74, 11.8 %), aplastic anemia (51, 8.1 %), plasma cell dyscrasia (45, 7.2 %), and vitamin B12 deficiency (40, 6.4 %) in Tohoku University Hospital. We made three primary findings as follows. First, the most common cause of macrocytic anemia is BMF. Second, lymphoid and solid malignancies are also common causes of macrocytosis. Third, macrocytic anemia may be classified into three groups: Group 1 (megaloblastic anemia and medications), which can exceed MCV 130 fL; Group 2 (alcoholism/liver disease, BMF, myeloid malignancy, and hemolytic anemia), which can exceed MCV 114 fL; and Group 3 (lymphoid malignancy, chronic renal failure, hypothyroidism, and solid tumors), which does not exceed MCV 114 fL. These conclusions were supported by the results from eight other hospitals.

Multicenter phase II clinical trial of nilotinib for patients with imatinib-resistant or -intolerant chronic myeloid leukemia from the East Japan CML study group evaluation of molecular response and the efficacy and safety of nilotinib.

BACKGROUND: Nilotinib is a second-generation tyrosine kinase inhibitor that exhibits significant efficacy as first- or second-line treatment in patients with chronic myeloid leukemia (CML). We conducted a multicenter Phase II Clinical Trial to evaluate the safety and efficacy of nilotinib among Japanese patients with imatinib-resistant or -intolerant CML-chronic phase (CP) or accelerated phase (AP). RESULTS: We analyzed 49 patients (33 imatinib-resistant and 16 imatinib-intolerant) treated with nilotinib 400 mg twice daily. The major molecular response (MMR) rate was 47.8% at 12 months among 35 patients who did not demonstrate an MMR at study entry. Somatic BCR-ABL1 mutations (Y253H, I418V, and exon 8/9 35-bp insertion [35INS]) were detected in 3 patients at 12 months or upon discontinuation of nilotinib. Although 75.5% of patients were still being treated at 12 months, nilotinib treatment was discontinued because of progressing disease in 1 patient, insufficient effect in 2, and adverse events in 9. There was no statistically significant correlation between MMR and trough concentrations of nilotinib. Similarly, no correlation was observed between trough concentrations and adverse events, except for pruritus and hypokalemia. Hyperbilirubinemia was frequently observed (all grades, 51.0%; grades 2-4, 29%; grades 3-4, 4.1%). Hyperbilirubinemia higher than grade 2 was significantly associated with the uridine diphosphate glucuronosyltransferase (UGT)1A9 I399C/C genotype (P = 0.0086; Odds Ratio, 21.2; 95% Confidence Interval 2.2-208.0). CONCLUSIONS: Nilotinib was efficacious and well tolerated by patients with imatinib-resistant or -intolerant CML-CP/AP. Hyperbilirubinemia may be predicted before nilotinib treatment, and may be controlled by reducing the daily dose of nilotinib in patients with UGT1A9 polymorphisms. TRIAL REGISTRATION: clinicaltrials.gov: UMIN000002201.

Hepatic portal venous gas associated with severe graft-versus-host disease of the gastrointestinal tract.

We report a 67-year-old woman who was diagnosed with hepatic portal venous gas associated with severe graft-versus-host disease (GVHD) of the gastrointestinal tract. The patient received allogenic peripheral blood stem cell transplantation from a haploidentical son against Philadelphia chromosome-positive acute lymphocytic leukemia. The patient developed grade 3 intestinal GVHD on day 90 from the transplantation. On day 149, she presented septic shock and computed tomography (CT) scan revealed hepatic portal venous gas (HPVG); an ileocecal resection was performed immediately. The damage of gastrointestinal mucosa by GVHD resulted in the invasion of gas-producing bacteria. Although HPVG-associated gastrointestinal GVHD is extremely rare, we should pay special attention to this pathogenesis.

[Sequential monitoring of plasma EBV-DNA level in a patient with EBV-positive Hodgkin lymphoma].

A 58-year-old woman was admitted to our hospital because of fever, systemic lymphadenopathy with abnormal Epstein-Barr virus (EBV) antibody titers, and a high EBV-DNA load in the serum. She had been diagnosed as possibly having chronic active EBV infection (CAEBV) during a previous hospitalization. The EBV-DNA load of the plasma (pEBV-DNA), examined at our hospital, was elevated to 1.8×10(4) copies/ml, whereas that of the peripheral blood mononuclear cells was 3.4×10(1) copies/µg DNA, which was not clearly elevated, unlike in cases with CAEBV. Biopsy of the cervical lymph node was performed and the diagnosis of mixed cellularity classical Hodgkin lymphoma, Stage4B was made. Hodgkin cells were positive for EBV. COPP therapy was started and pEBV-DNA decreased drastically. The treatment was followed by ABVD therapy and pEBV-DNA turned negative after one course of ABVD therapy. She achieved complete response after 4 courses of the treatment. Reports from abroad indicate that pEBV-DNA parallels the disease state of EBV-positive Hodgkin lymphoma. Our results were consistent with these reports, and demonstrated that, in a Japanese patient, EBV-DNA load and its localization in the peripheral blood fractions could be useful tools for diagnosis as well as evaluating the disease status.

Fournier's gangrene in a patient receiving treatment for idiopathic thrombocytopenic purpura.

We report the case of a 68-year-old man who was diagnosed with Fournier's gangrene (FG), which developed during immunosuppresive treatment for idiopathic thrombocytopenic purpura (ITP). The patient was administered steroids for ITP but on the 36th day, he developed FG and septic shock. We initiated antibiotic treatment and drained a periproctal abscess immediately. On day 53, extensive drainage to progressive FG and a splenectomy was performed, following which both FG and thrombocytopenia improved. This is the first case of FG has developing in a ITP patient. It appears that high-dose immunoglobulin therapy and splenectomy should be considered earlier especially for a patient complicated with FG.

[Serum free light-chain assay for nonsecretory multiple myeloma with light chain cast nephropathy and light chain deposition disease].

Quantitative assay for serum free light chains (sFLC) is reported as a useful test for diagnosis and monitoring of patients with nonsecretory multiple myeloma (NSM). We performed serial sFLC assays in a patient with NSM with light chain cast nephropathy (LCCN) and light chain deposition disease (LCDD). After 3 cycles of VAD induction therapy, while plasma cells in the marrow decreased from 93.0% to 0.2%, sFLCkappa/lambda ratio remained abnormal. Flow cytometry assay also showed that these plasma cells were CD19 negative. After the subsequent high dose melphalan therapy followed by autologous peripheral blood stem cell transplantation (PBSCT), the sFLCkappa/lambda ratio returned to normal and the patient achieved a stringent complete response (sCR). One year after PBSCT, the patient remained in sCR with improved renal function. The quantitative FLC assay was useful for the diagnosis and monitoring of NSM and LCDD in this patient.