Isao Maekawa

Induction therapy consisting of alternating cycles of ranimustine, vincristine, melphalan, dexamethasone and interferon alpha (ROAD-IN) and a randomized comparison of interferon alpha maintenance in multiple myeloma: a co-operative study in Japan.

This pilot study evaluated the efficacy of a new combination chemotherapy with a newly developed nitrosourea derivative ranimustine and evaluated the efficacy of interferon α (IFN‐α) maintenance in previously untreated patients with multiple myeloma (MM). The induction therapy (ROAD‐IN) was a 6‐week regimen consisting of chemotherapy with ranimustine, vincristine (Oncovin), melphalan (Alkeran) and dexamethasone starting on day 1 and IFN‐α, which was administered three times weekly for 3 weeks starting on day 22. This was repeated for three cycles. The responders were subsequently randomized into two groups that received or did not receive IFN‐α as maintenance therapy. Of the 164 patients registered, 161 were evaluated. An objective response to induction therapy was seen in 75% of patients; complete remission (CR) in 38 (24%) and partial remission (PR) in 82 (51%). The median survival for all patients was 3·6 years from registration. The survival of responders (CR + PR) was significantly better than that of non‐responders (median survival 4·3 years vs. 1·4 years; 7‐year survival rate 32% vs. 9%; P < 0·0001). The IFN‐α maintenance did not show any advantage for either response duration or survival. This pilot study demonstrated that a comparatively short period of induction therapy with the ROAD‐IN regimen produced a rather high response rate and a similar survival rate to those achieved with other longer induction regimens, and that good responders to the initial therapy survived significantly longer than non‐responders.

Primary biliary cirrhosis associated with idiopathic thrombocytopenic purpura.

A case of primary biliary cirrhosis (PBC) associated with idiopathic thrombocytopenic purpura (ITP) is reported. The patient is a 59-year-old man. When he was 49 years old, he was diagnosed with ITP and received steroid therapy that successfully increased platelet numbers. However, the steroid therapy failed to normalize the elevated gamma-glutamyl transpeptidase. Ten years after this episode, he suffered from general itching and malaise and exhibited a gradual increase of serum biliary enzyme levels. Immunologically, IgM was increased and anti-mitochondrial antibody was positive. Histological findings of liver needle biopsy showed chronic non-suppurative destructive cholangitis, confirming the diagnosis of PBC. To date, very few PBC cases associated with ITP have been reported. Our case is the second one in Japan. PBC and ITP in our patient seemed to develop simultaneously, but the effect of steroid therapy on the two conditions was different. This result suggests that the autoimmune process may have been different in PBC and ITP in the present patient.

Insertion (21;8)(q22;q22q22) : a masked t(8;21) in a patient with acute myelocytic leukemia

A 43-year-old man was diagnosed with acute myelocytic leukemia with cellular maturation (AML-M2, according to the French-American-British classification criteria). A cytogenetic study with a G-banding method initially reported the karyotype as 45,X,-Y; however, dual-color, dual-fusion fluorescence in situ hybridization (FISH) with probes for the AML1 and the ETO genes showed an unusual pattern of signals, presenting one fusion signal on chromosome 21. Molecular study by reverse transcriptase polymerase chain reaction revealed the presence of a typical AML1/ETO chimeric gene. FISH with whole-chromosome painting probes targeting chromosomes 8 and 21 revealed insertion of part of 8 chromosome into the long arm of chromosome 21. We concluded that complicated translocations involving chromosomes 8 and 21 in this patient resulted in the development of the chimeric gene, AML1/ETO, on the long arm of chromosome 21. This aberrant location of AML1/ETO gene and the final karyotype of 45,X,-Y,ins(21;8)(q22;q22q22) could not be determined without molecular analysis. This abnormality is considered a masked t(8;21).

Effects of rhG-CSF on Infection Complications and Impaired Function of Neutrophils Secondary to Chemotherapy for Non-Hodgkin's Lymphoma

It has been previously demonstrated that the administration of recombinant human granulocyte-colony stimulating factor (rhG-CSF) ameliorates the decrease of the polymorphonuclear neutrophils (PMNs) count after the cytotoxic chemotherapies, thereby reducing the infection complications associated with neutropenia. In this multi-center study, we studied the prophylaxtic effect of rhG-CSF administration on infection complications in patients with non-Hodgkin malignant lymphoma, who received cytotoxic chemotherapies (CHOP or ProMACE/CytaBOM). rhG-CSF administration reduced the frequency of infection complications, and there was no obvious difference in its frequency between the CHOP-treated and the ProMACE/CytaBOM-treated groups when administered with rhG-CSF, thereby indicating that third generation therapy for NHL may be safely completed in Japanese in combination with rhG-CSF administration. Furthermore, we investigated both the in vitro and the in vivo effects of rhG-CSF on the function of PMNs in patients with NHL and healthy donors, and revealed that the administration of rhG-CSF for NHL patients receiving cytotoxic chemotherapy brought on an improvement of the production of active oxygen but did not affect serum levels of IFNs, IL-1-beta, and IL-6, inspite of a slight elevation of TNF-alpha. Consistent with these results, in vitro treatment of PMNs with rhG-CSF induced no significant production of these inflammatory cytokines and their mRNA expressions. Furthermore, rhG-CSF administration showed no significant effects in vivo on the expression of CD11a, CD11b and LECAM-1 on PMNs and integrins on platelets.

An autopsy case of triple cancers including signet-ring cell carcinoma of the breast —Report of a rare case with reference to a review of the literature—

A 67 year old Japanese woman who had been suffering from general fatigue was diagnosed as having metastasis of signet-ring cell carcinoma of the bone marrow from a biopsied specimen. A clinical effortive search to the systemic organs revealed a tumor of 4×3 cm in size in the lower part of her left breast, which was subsequently diagnosed as the primary site histopathologically. The patient was immediately treated surgically, however, her general condition generally deteriorated and she expired 5 months after the operation. Autopsy revealed dissemination of tumor cells in the bone marrow, bilateral pleura, and soft tissue around the operated site. The autopsy additionally revealed squamous cell carcinoma of keratinizing type in the uterine cervix and well differentiated tubular adenocarcinoma in the gallbladder. A review of the literature revealed this case to be the first reported case of triple cancers including signet ring-cell carcinoma of the breast, proven by autopsy in Japan.

Administration of rhG-CSF Increases Complete Remission Rates After CHOP and ProMACE/CytaBOM for Non-Hodghn's Lymphoma: A Pilot Study

To evaluate the clinical effects of the administration of recombinant human granulocyte-stimulating factor (rhG-CSF) post chemotherapy for patients with advanced-staged intermediate-grade or high-grade non-Hodgkins malignant lymphoma (NHL), we conducted this multicenter study and compared the responses between both the regimens, CHOP as a first-generation chemotherapy and ProMACE/CytaBOM as a third-generation chemotherapy, when combined with the rhG-CSF administration. In this multicenter study, where forty patients were registered, patients in both the CHOP and ProMACE/CytaBOM groups were treated with the original regimen designs without the necessity of reducing drug dosages when combined with the administration of rhG-CSF. The administration of rhG-CSF post both of the cytotoxic therapies brought about much higher rates of complete remission in both the groups (CHOP, 75 percent; ProMACE/CytaBOM, 75 percent), as compared with those of the previous study without the rhG-CSF administration. Regarding res...

An autopsy case of malignant fibrous histiocytoma of the mediastinum presenting multiple metastases to the small intestine and to the brain

SummaryAn autopsy case of malignant fibrous histiocytoma (MFH) of the mediastinum in a 25-year-old Japanese man is described. He initially complained of general fatigue and intermittent tarry stool, and was radiographically revealed to have a huge mass within the mediastinum as well as multiple nodules within the abdominal cavity, respectively. The mediastinal tumor could not be resected because of direct tumor invasion into surrounding tissues. Within the abdominal cavity, three distinct tumor nodules were discovered in the jejunum, which could be resected surgically. Histopathologically, the components of both lesions were very similar, and the present case was interpreted as multiple metastases of mediastinal MFH to the intestinal wall. In spite of various kinds of treatment, the mediastinal tumor rapidly enlarged, causing SVC syndrome. Brain CT findings suggested multiple metastases which were considered to be the cause of death. Autopsy confirmed that the main tumor nodule was located within the mediastinum, with brain metastases. The present case of mediastinal MFH is considered to be the youngest case as well as the first case presenting intestinal metastases.