The number of hematopoietic stem cell transplantations and recipients with late complications from transplantation are both increasing; therefore, we investigated the status of the long-term follow-up system for hematopoietic stem cell transplantation survivors in Japan using a mail questionnaire; 100 of 194 institutions replied. The median examination time for each patient was 12.5 min. Five percent of institutions had an outpatient transplantation clinic, 1% had a manual for long-term follow-up after stem cell transplantation, and 11% used NIH criteria for the diagnosis of chronic GVHD. The lack of human resources, such as doctors, nurses, and other co-medical staff for transplant patients, was a structural problem. In addition, the development of guidelines for Japanese patients and staff education are also required in the clinical process. Thus, a long-term follow-up system, training of human resources, and appropriate reallocation of funds for medical services are required.

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Although high-dose chemotherapy supported by autologous peripheral blood stem cell transplantation (auto-PBSCT) is the standard approach for younger patients with multiple myeloma, some of them still show a poor prognosis. We attempted to define a high-risk group among 32 patients who received auto-PBSCT between August 2000 and July 2007 in our hospital. In conventional metaphase cytogenetics (G-banding), chromosome abnormalities (CA), hypodiploidy, and 13 or 13q deletion (Gd13) were noted in 27.6, 17.2, and 19.4% of patients, respectively. In a FISH study, del(17p) (Fd17p) and t(4;14) were noted in 12.5 and 9.4% of patients, respectively. Prognostic analyses of patients with these abnormal chromosomes revealed that those with CA, hypodiploidy, Gd13, and t(4;14) showed a poorer survival at 3 years compared to those without them: 42.9 vs. 95.2% (p=0.0072), 25.0 vs. 91.5% (p=0.0056), and 40.0 vs. 91.8% (p=0.0245), 0 vs. 89.3% (p<.0001), respectively. When we defined patients showing at least one of CA, hypodiploidy, Gd13, Fd17p, and t(4;14) as a “high-risk group”, they showed a poorer overall (23.9 vs. 106.1 mo., p=0.0011) and progression-free (13.5 vs. 25.6 mo., p=0.0095) survival compared to a non-high-risk group. This study indicated that chromosome analysis has a prognostic value in patients with multiple myeloma receiving auto-PBSCT.

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We retrospectively analyzed the clinical outcome of dasatinib in 7 patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) resistant or intolerant to imatinib. Three patients with chronic phase CML and two patients with Ph+ALL achieved major molecular response, however, two CML patients in accelerated phase (AP)/blast crisis (BC), did not. Grade≥3 pancytopenia was seen in four patients. Among these, two AP/BC-CML patients required interruption/or dose reduction of dasatinib. As for nonhematologic adverse events, pleural effusion was seen in one patient and cytomegalovirus (CMV) colitis was observed in two patients. No patients who had been intolerant to imatinib experienced the same nonhematologic toxicity following treatment with dasatinib. We identified three patients who developed peripheral lymphocytosis, identified as natural killer cells or cytotoxic T-cells based on their large granular lymphocyte (LGL) morphologies and immunophenotypic profiles, out of six patients receiving dasatinib therapy. All three cases that developed LGL lymphocytosis achieved optimal molecular response, two of the patients, however, had pleural effusion and CMV colitis, respectively. Dasatinib inhibits off-target kinases, which may result in unexpected drug responses.

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Factors that affect the response of multiple myeloma patients to thalidomide were evaluated in 40 patients who were not eligible for chemotherapy (untreated: 14, relapse/refractory: 26). The complete response (CR) rate was 2.5%; partial response (PR) 50.0%; minimal response (MR) 25.0%; no change (NC) 12.5%; and progressive disease 10.0%. The response to thalidomide could be evaluated after four weeks of treatment. Significantly higher responses were associated with untreated patients, patients with combined use of thalidomide plus dexamethasone, and patients with kappa light chain. Patients who responded well to thalidomide showed a significantly higher progression-free survival (PFS) rate. In patients with kappa light chain, PFS and overall survival rates were significantly higher than those with lambda light chain. Frequent adverse reactions were numbness (47.5%), constipation (32.5%), and eruption (30.0%). In patients previously treated with vincristine, numbness occurred in a significantly higher percentage of patients.

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Marfan syndrome (MFS) is caused by mutations in the gene encoding fibrillin. A 35-year-old man with MFS visited a local physician because of a sore throat. His left tonsil gradually became swollen and he was referred to our department. Histopathological examination of tonsil biopsy specimens showed diffuse proliferation of lymphoma cells with large nuclei. The tumor cells showed CD5+, CD10+, CD20+, BCL-6+, and MUM-1-. Based on these findings, the patient was diagnosed with CD5+ CD10+ diffuse large B-cell lymphoma (DLBCL). Chemotherapy combined with rituximab was administered and complete response was achieved. CD5+ DLBCL comprises approximately 5∼10% of DLBCLs. In addition, CD5+ CD10+ DLBCL comprises about 5% of CD5+ DLBCLs. There may be a relationship between MFS and B-cell lymphoma because mutations in the gene encoding the receptor of transforming growth factor-beta (TGF-β) have been implicated in the pathogenesis of MFS and downregulation of TGF-β receptor expression has been described in the pathology of B-cell lymphoma.

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We report a 4-year-old girl who presented with acute onset of hemophagocytic syndrome (HPS) after induction therapy and HPS relapsed immediately after reduced-intensity cord blood transplantation (RI-CBT) for relapse of acute lymphoblastic leukemia. The patient underwent CBT from 2 locus-mismatched donor, after reduced-intensity conditioning therapy consisting of fludarabine, melphalan, and total body irradiation 4Gy. Prednisolone and cyclosporine were administered for prophylaxis against graft-versus-host disease. Bone marrow examination on day 20 revealed activated macrophages displaying hemophagocytosis. The origin of macrophages was 2^nd donor derived. After administration of steroids, intravenous immunoglobulin and VP-16, the patient exhibited complete chimerism and remained in complete remission for over one year.

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A 38-year-old man was admitted to our hospital because of continuous fever and right facial palsy. He was diagnosed as HIV positive. Abdominal CT scan showed a large mass in the ascending colon. Gallium scintigraphy demonstrated increased uptake in the ascending colon. Colonoscopy was performed and histological examination of the colon tumor revealed Burkitt's lymphoma (BL). He received highly active anti-retroviral therapy (HAART) and his facial palsy improved. Because CD4 count was significantly low at 31/μl, he was treated with dose-adjusted EPOCH (DA-EPOCH) combined with HAART. Although the tumor was decreased in size by DA-EPOCH, we changed to the combination of hyper-CVAD/MTX-Ara-C alternating therapy with HAART in order to increase dose intensity. Six cycles of hyper-CVAD/MTX-Ara-C were performed and complete remission was obtained. In the HAART era, the survival of patients with AIDS-related diffuse large cell lymphoma (DLCL) improved dramatically, whereas the survival of similarly treated patients with AIDS-related BL remained poor. Our case suggests that intensive chemotherapy with hyper-CVAD/MTX-Ara-C combined with HAART may be well tolerated and effective in AIDS-related BL.

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Reactivation of hepatitis B virus (HBV) has been recognized as one of the most serious complications in patients receiving chemotherapy with rituximab. From October 2007 to December 2008, rituximab was administered to 123 B-cell lymphoma patients in our institute. Four patients with positive hepatitis B surface antigen (HBsAg) received preemptive entecavir, and none of them developed HBV reactivation. For 26 patients whose hepatitis B surface antibody (HBsAb) and/or hepatitis B core antibody (HBcAb) were positive, HBV-DNA was monitored for one year after completion of chemotherapy. During this period, HBV reactivation was observed in two patients. Hepatitis was prevented in one patient by the administration of entecavir at the time HBV-DNA turns positive. Another developed de novo hepatitis B due to failure of monitoring. Preemptive entecavir for HBsAg positive patients and HBV-DNA monitoring for HBsAb and/or HBcAb positive patients seem to be effective.

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