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Extended post-therapy long-term survival of patients with diffuse large B cell lymphoma (DLBCL) may also lead to an increase of late adverse events. We retrospectively investigated the frequency and clinical manifestation of second primary malignancy (SPM) after rituximab-containing immunochemotherapy in patients with DLBCL treated at seven institutes belonging to the Kyoto Clinical Hematology Study Group (KOTOSG) from the perspective of the existence of past or synchronous cancer history. In a median follow-up period of 899 days, 69 SPMs were observed in 58 of 809 patients. The most frequent SPM was gastric cancer, followed by lung cancer and colorectal cancer. The cumulative incidence of SPM increased steadily over time and was not significantly influenced by the presence or absence of past or synchronous cancer history. Our study suggests the need for careful attention to SPM in patients with DLBCL in daily practice.

Delayed platelet engraftment (DPE) is occasionally observed despite prompt neutrophil engraftment after autologous peripheral blood stem cell transplantation (auto-PBSCT). To identify risk factors for DPE and to develop a simple and clinically applicable system for predicting the time required for platelet recovery, we conducted a multi-institutional retrospective study in 144 patients with B-cell non-Hodgkin lymphoma who underwent auto-PBSCT. In a median observation period of 930 days (range: 25-5272 days), 139 patients successfully achieved platelet engraftment (≥50.0 × 10 9 /L). The median duration for platelet engraftment was 19 days, and 130 patients had platelet engraftment within 40 days after auto-PBSCT; however, the other 14 patients failed to achieve platelet engraftment within 60 days. These 14 patients with DPE required a significantly greater number of apheresis procedures and had a lower pre-apheresis absolute lymphocyte count (PA-ALC) compared to those without DPE. Importantly, multivariate analysis revealed that the number of transplanted CD34 + cells (≤2.0 × 10 6 /kg), number of required apheresis procedures (≥3 days), and PA-ALC (≤1.0 × 10 9 /L) were independently associated with a longer time for platelet engraftment after auto-PBSCT. By incorporating these three independent factors as variables, we generated a new scoring system for prediction of the time and probability for platelet engraftment after auto-PBSCT.

A healthy 33-year-old man presented with a short history of viral infection and recent petechiae. Examination of the blood showed a profound thrombocytopenia. He was diagnosed as having cytomegalovirus infection by serological examination. A high level of platelet-associated immunoglobulins was demonstrated suggesting an immune basis for the thrombocytopenia and we, therefore, treated the patient with bolus methylprednisolone and gamma-globulin, resulting in prompt recovery. Recognition for CMV-induced thrombocytopenia is important for early diagnosis.

We describe 2 elderly patients with Human herpesvirus 8 (HHV-8)/Kaposi sarcoma herpes virus negative malignant effusion lymphoma showing pan-B-cell immunophenotyping markers and successfully treated with a chimeric anti-CD20 IgG1 monoclonal antibody, rituximab. A 90-year-old man and an 87-year-old woman were hospitalized because of pleural effusions. They were diagnosed as having malignant effusion lymphoma on the basis of cytologic and flow cytometric findings of effusions, revealing involvement of atypical lymphoid cells and expression of CD19 and CD20. The former case was intolerant of chemotherapy because of toxicity. Using the conventional dose of rituximab, they showed neither intolerance nor adverse effects and their pleural effusions decreased immediately. Any sign of disease progression was not noted in either of the patients. They were negative for a HHV-8 infection and had no history of pyothorax. This type of lymphoma was not compatible with primary effusion lymphoma (PEL) defined by World Health Organization Classification of Tumors or pyothorax-associated lymphoma. We diagnosed these patients as having "HHV-8 negative malignant effusion lymphoma". HHV-8 negative malignant effusion lymphoma may be a new clinicopathologic and biologic entity. Because most of the cases were positive for pan-B-cell markers, rituximab may be a promising agent for the treatment.

The present study aimed to characterize the clinical and molecular-cytogenetic features of non-Hodgkin's lymphoma (NHL) with double translocation of the immunoglobulin heavy chain (IGH) gene. G-banding analysis, fluorescence in situ hybridization (FISH) with the IGH (Cgamma and VH) and oncogene (c-MYC, BCL1, BCL2, and BCL6) probes, and long-distance polymerase chain reaction (LD-PCR) were performed on 6 patients with B-cell lymphoma, one with angioimmunoblastic T-cell lymphoma, and one with acute lymphoblastic leukemia (ALL) with B-cell phenotype. G-banding analysis detected two different 14q32 translocations, t(14,18) and add (14)(q32) in a patient with ALL. Two distinct partners of double IGH translocation identified by FISH were as follows: c-MYC + BCL2 in 3 patients, c-MYC + BCL1 in 2, c-MYC + BCL6 in one, BCL2 + 9q22 in one, and 1q21 + 6q27 in one. Colocalization of BCL1 and c-MYC probes was demonstrated in a patient with mantle cell lymphoma. LD-PCR detected c-MYC/Cmu, c-MYC/Calpha and BCL6/Cmu, and c-MYC/Calpha fusion in each one patient. Seven of 8 patients showed high serum LDH. Central nervous system and leukemic involvement was observed in 5 and 6 patients, respectively. Median survival time of patients with c-MYC/IGH translocation was 9 months. The results defined a clinical subset of B-cell lymphoma/leukemia showing extremely poor prognosis. C-MYC/IGH translocation is possibly an evolutionary alteration following the primary IGH translocation with BCL1, BCL2, or BCL6. Furthermore, FISH identified one novel (9q22) and one cryptic chromosomal breakpoints (6q27) involved in IGH translocation.

We describe a patient with chronic myelogenous leukemia who developing severe intestinal bleeding after allogeneic peripheral blood stem cells transplantation (allo-PBSCT). PBSC were obtained from an HLA one-locus mismatch sibling donor. On day 26 after PBSCT, although there was no sign of graft-versus-host disease (GVHD) in either the skin or the liver, diarrhea and severe intestinal bleeding occurred. The histopathological examination of the colon revealed complete denudation of the epithelial cells of the mucosa and no obvious apoptosis. Neither red cell fragments nor hemorrhagic diathesis was seen during this episode and the patient was diagnosed as having GVHD. Methylpredonisolone followed by FK506 may be effective in controlling intestinal bleeding and was used in our patient. Acute GVHD involving only the intestine has rarely been described but when using HLA-mismatched PBSCs, acute GVHD may occur severely and atypically., (Copyright 2004 Taylor and Francis Ltd.)

Myelodysplastic syndrome (MDS) consists of a heterogeneous group of acquired hematopoietic stem cell disorders, characterized by bone marrow failure and leukemic transformation. Since hematological manifestations and clinical outcomes vary widely among MDS patients, a considerable number of studies have tried to identify the prognostic parameters for the stratification of patients into different risk groups. Based on reported risk-based studies, the International Prognostic Scoring System (IPSS) was proposed as a reliable risk assessment method for primary MDS patients, and several validating studies have clarified its usefulness. Critical prognostic parameters of the IPSS consist of chromosome findings, the percentage of marrow blasts, and the number of peripheral blood cytopenias. Although other laboratory findings, including several molecular alterations, have been identified as convincing prognostic factors in MDS, these molecular configurations were not selected as prognostic parameters in the IPSS, because analysis for these alterations were not routinely available for the management of patients with MDS. Because recent advances in molecular genetics may make it available as a routine work-up of MDS in the future, we discuss potential improvement of the IPSS by the addition of molecular analysis to the system, with particular reference to the configuration of the TP53 gene.

We describe a patient with natural killer (NK)/T cell lymphoma who relapsed after autologous peripheral blood stem cell transplantation (auto-PBSCT) and was successfully treated with Escherichia coli (E. coli) and Erwinia L-asparaginase. A 38-year-old male patient with ulcerated tumor at the left thigh was diagnosed as having nasal type NK/T cell lymphoma on the basis of histopathological and flowcytometric findings of tumor, revealing diffuse infiltration of atypical lymphoid cells into blood vessels and expression of CD7 and CD56 antigens, but not CD3. He had tumor infiltration in the bone marrow and at the right lower lung field. After five cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) therapy, the patient achieved complete remission and received high-dose chemotherapy with auto-PBSCT, although the tumor recurred in the right leg 10 months later. Despite salvage chemotherapy, followed by local irradiation and surgical amputation, a tumor recurred at the left upper gingiva 10 days after. Using E. coli L-asparaginase (6000 U/m2/day), the tumor regressed, fever was alleviated and the serum lactate dehydrogenase decreased to normal range after several days. The asparagine synthetase expression in tumor cells was immunohistochemically negative on paraffin-embedded tissues. Because of the anaphylactoid reaction developing after E. coli L-asparaginase, alternative Erwinia L-asparaginase (6000 U/m2/day) was administered, resulting in regression of tumor and fever lysis. L-asparaginase is a promising agent for the treatment of NK/T cell lymphoma.

We describe a patient with acute lymphoblastic leukemia (ALL, L2) who relapsed with multiple bone lesions after allogeneic bone marrow transplantation (allo-BMT). Allo-BMT was performed from an HLA-identical sibling during the first hematological complete remission (CR). Minimal residual disease (MRD) assessed by polymerase chain reaction (PCR) with primers for T cell receptor delta (TCRdelta) gene became positive in the bone marrow sample on day 46 after allo-BMT. On day 113, the patient complained of a painful tumor at the right clavicle. The examination of biopsy specimen revealed infiltration of leukemic cells. After partial response was achieved by local radiotherapy, disseminated bone lesions were demonstrated by 99mTC scintigraphy scan, followed by bone marrow relapse on day 137. The patient died of cardiac tamponade on day 236 after Allo-BMT. MRD assessed by PCR assay for TCRdelta gene in the bone marrow is useful for the prediction of extramedullary as well as medullary relapse after BMT.

Mutations of the TP53 tumor suppressor gene, contributing to the development and progression of a wide variety of human malignancies, are found in some of the patients with myelodysplastic syndromes (MDS). Previous reports revealed that TP53 mutations were found in 0-25% of patients with MDS and are closely associated with a complex abnormal karyotype including such chromosomal losses as -5/5q-, -7/7q- and/or 17p-, which are known to be frequent in therapy-related leukemias. We have also detected TP53 mutation in 10 (14%) of 70 patients with MDS. All of the mutations were detected at the time of diagnosis, which suggest the TP53 mutation may play a role in the development of MDS. Those patients with a TP53 mutation had a poor prognosis regardless of leukemic transformation or not. The reported mutational spectra of TP53 in MDS and ANLL differ from those of colon and lung cancers. Compared with other hematological disorders, the spectrum of TP53 mutations in MDS and ANLL is assumed to be associated with pathogenic exposure to known or unknown carcinogens, as suggested by the chromosomal findings. Further studies are required to clarify the pathogenesis of this heterogenous disease entity.