A Soluble Form of P Selectin Glycoprotein Ligand 1 Requires Signaling by Nuclear Factor Erythroid 2-Related Factor 2 to Protect Liver Transplant Endothelial Cells Against Ischemia-Reperfusion Injury.

Liver endothelial cell (LEC) damage is essential in the pathogenesis of ischemia-reperfusion injury (IRI) in transplant recipients. We analyzed the mechanism of LEC resistance against IRI by using a novel recombinant soluble form of P selectin glycoprotein ligand 1, tandem P selectin glycoprotein ligand immunoglobulin (TSGL-Ig), in a mouse model of hepatic cold preservation (4°C in University of Wisconsin solution for 20 h) and syngeneic orthotopic liver transplantation (OLT). Unlike controls, TSGL-Ig protected orthotopic liver transplants against ischemia-reperfusion (IR) stress, shown by depressed serum alanine aminotransferase levels, well-preserved hepatic architecture, and improved survival (42% vs. 92%). TSGL-Ig suppressed neutrophil/macrophage sequestration and proinflammatory cytokine/chemokine programs in OLT. Treatment with TSGL-Ig mitigated LEC activation (P and E selectin, VCAM-1 and intercellular adhesion molecule 1 expression). In parallel in vitro studies, TSGL-Ig diminished cellular damage in H2 O2 -stressed LEC cultures (lactic acid dehydrogenase and alanine aminotransferase levels). Increased thioredoxin, glutamate-cysteine ligase, NAD(P)H quinone dehydrogenase 1, and hypoxia-inducible factor 1α expression, along with transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), implied that TSGL-Ig exerts antioxidant functions in IR-stressed OLT and H2 O2 -stressed LECs. Indeed, Nrf2-deficient livers suffered fulminant IRI compared with WT despite concomitant TSGL-Ig therapy. Thus, TSGL-Ig is not only acting as a competitive antagonist blocking leukocyte migration into IR-stressed liver, but it may also act directly as an agonist stimulating Nrf2-mediated cytoprotection in LECs. This study supports the role of P selectin signaling in hepatic homeostasis in OLT, with broad implications for tissue damage conditions.

Impact of Subnormothermic Machine Perfusion Preservation in Severely Steatotic Rat Livers: A Detailed Assessment in an Isolated Setting.

The current drastic shortage of donor organs has led to acceptance of extended-criteria donors for transplantation, despite higher risk of primary nonfunction. Here, we report the impact of subnormothermic machine perfusion (SMP) preservation on the protection of >50% macrosteatotic livers. Dietary hepatic steatosis was induced in Wistar rats via 2-day fasting and subsequent 3-day re-feeding with a fat-free, carbohydrate-rich diet. This protocol induces 50-60% macrovesicular steatosis, which should be discarded when preserved via cold storage (CS). The fatty livers were retrieved and preserved for 4 h using either CS in histidine-tryptophan-ketoglutarate or SMP in polysol solution. Graft functional integrity was evaluated via oxygenated ex vivo reperfusion for 2 h at 37°C. SMP resulted in significant reductions in not only parenchymal alanine aminotransferase (p < 0.001), but also mitochondrial glutamate dehydrogenase (p < 0.001) enzyme release. Moreover, portal venous pressure (p = 0.047), tissue adenosine triphosphate (p = 0.001), bile production (p < 0.001), high-mobility group box protein-1 (p < 0.001), lipid peroxidation, and tissue glutathione were all significantly improved by SMP. Electron microscopy revealed that SMP alleviated deleterious alterations of sinusoidal microvasculature and hepatocellular mitochondria, both of which are characteristic disadvantages associated with steatosis. SMP could protect 50-60% macrosteatotic livers from preservation/reperfusion injury, and may thus represent a new means for expanding available donor pools.

A randomized crossover study comparing patient preference for tamsulosin and silodosin in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia.

Patient preference for benign prostatic hyperplasia (BPH) treatment with the α(1)-blockers, tamsulosin or silodosin, was compared using patient-reported outcomes. Japanese patients with lower urinary tract symptoms associated with BPH were randomly allocated to either the T-S group (tamsulosin 0.2 mg orally once daily for 4 weeks then silodosin 4 mg orally twice daily for 4 weeks) or the S-T group (silodosin 4 mg orally twice daily for 4 weeks then tamsulosin 0.2 mg orally once daily for 4 weeks). The primary endpoint was the preferred drug for treatment continuation at 8 weeks, determined by a patient-reported questionnaire. In total, 102 patients (mean age 70.3 years) were enrolled and 84 (n = 42 per group) completed the study. A significant difference was observed between the proportion of patients who preferred tamsulosin (59/84 patients; 70.2%) and those who preferred silodosin (18/84 patients; 21.4%). A major reason for preference of either drug was 'good efficacy'. Incidence of adverse effects was significantly lower with tamsulosin (3/91 patients; 3.3%) than with silodosin (25/88 patients; 28.4%). These findings indicate that tamsulosin is very effective for BPH, has few adverse effects and that patients want to continue to use it.

Diagnosis of bone metastasis in men with prostate cancer by measurement of serum ICTP in combination with alkali phosphatase and prostate-specific antigen.

AIMS: Carboxy-terminal telopeptide of type I collagen (ICTP) is a parameter of bone absorption, and has recently been introduced to monitor bone metastases. The aim of this retrospective study was to investigate the potential of ICTP as a candidate serum marker of bone metastasis in prostate cancer. MATERIALS AND METHODS: Serum markers in 155 men pathologically diagnosed with prostate cancer were measured. The serum levels of ICTP, prostate-specific antigen (PSA), and alkali phosphatase (ALP) were compared to assess the extent of disease (EOD) scores from bone scans and then analysed statistically. RESULTS: The serum ICTP levels were not well correlated with the EOD scores in the total group of men, men newly diagnosed with prostate cancer, or men previously diagnosed with prostate cancer who were followed up. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of ICTP (cut-off value, 5.0 ng/ ml) of the men newly diagnosed with prostate cancer were 78.6%, 88.0%, 78.6%, and 88.0%, respectively. In these men, the specificity and PPV of ALP (cut-off value, 335 IU/l) were 100%, whereas the sensitivity and NPV of PSA (cut-off value, 40 ng/ml) were 100% in this study. The serum levels of ICTP in the men with low ALP (< 335 IU/l) and high PSA (> or = 40 ng/ ml) clearly separated the men with or without bone metastasis, as judged by bone scans. CONCLUSION: We found that the ICTP is not a superior serum marker for bone metastases compared with ALP or PSA. Our study suggests, however, that the ICTP measurement is useful in a certain subset of men with the combination of PSA and ALP in distinguishing men with bone metastasis from those without.

Efficient ex vivo generation of human dendritic cells from mobilized CD34+ peripheral blood progenitors.

We tried to efficiently generate human dendritic cells (DCs) from CD34+ peripheral blood hematopoietic progenitor cells mobilized by high-dose chemotherapy and subsequent administration of granulocyte colony-stimulating factor, using a liquid suspension culture system. Among various combinations, the combination of c-kit ligand, flt-3 ligand, c-mpl ligand (TPO), and interleukin (IL)-4 most potently generated the number of CD1a+CD14- DCs in cultures containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor alpha (TNF-alpha). The delayed addition of IL-4 on day 6 of culture gave rise to an additional increase in the yield of CD1a+CD14-DCs that were characterized by the expression of HLA-ABC, HLA-DR, CD80, CD86, and CD83. The majority of the sorted CD1a-CD14+ cells derived from 6-day culture of CD34+ cells gave rise to CD1a+CD14- DCs and CD1a-CD14+ macrophages on day 12 of culture in the presence and absence of IL-4, respectively. These findings suggest that IL-4 promotes the differentiation of CD1a- CD14+ cells derived from mobilized CD34+ peripheral blood hematopoietic progenitors to CD1a+ CD14- DCs. The majority of these DCs expressed CD68 but not the Langerhans-associated granule antigen, a finding that suggests they emerge through the monocyte differentiation pathway. The addition of TPO and IL-4 to cultures did not affect the potential of DCs to stimulate the primary allogeneic T-cell response. These findings demonstrated that the combination of c-kit ligand plus flt-3 ligand plus TPO with GM-CSF plus TNF-alpha, followed by IL-4, is useful for ex vivo generation of human DCs from mobilized CD34+ peripheral blood progenitors.

Analysis of prognostic factors in newly diagnosed patients with acute promyelocytic leukemia: the APL92 study of the Japan Adult Leukemia Study Group (JALSG).

All-trans-retinoic acid (ATRA) has been incorporated in front-line therapy for newly diagnosed acute promyelocytic leukemia (APL). We conducted a multicenter study of differentiation therapy with ATRA alone or in combination with chemotherapy followed by intensive postremission chemotherapy in patients with APL (the JALSG APL92 study), and analyzed prognostic factors to increase the cure rate in our subsequent trial. From 1992 to 1997, adult patients with newly diagnosed APL received oral ATRA 45 mg/m2 daily alone until complete remission (CR) if initial leukocyte counts were < 3.0x10(9)/l, and ATRA daily plus daunorubicin (DNR) 40 mg/m2x3 days plus enocitabine (BHAC) 200 mg/m2x5 days if leukocyte counts were > or =3.0 x 10(9)/l. If peripheral blasts exceeded 1.0x10(9)/l during therapy, DNRx3 days plus BHACx5 days was added. After CR was achieved, three courses of consolidation and six courses of maintenance/intensification chemotherapy were administered. Of 376 patients enrolled, 369 were evaluable (median age 46 years, range 15-86 years; median leukocyte counts 2.0x10(9)/l), and 333 (90%) achieved CR (94% of patients treated with ATRA alone, 88% with ATRA plus later chemotherapy, 89% with ATRA plus initial chemotherapy, and 86% with ATRA plus initial and later chemotherapy). At a median follow-up of 45 months, the predicted 6-year overall and event-free survival (EFS) rates for all patients were 65% and 52%, respectively. Favorable prognostic factors for CR were younger age, no or mild purpura, high serum total protein level, low lactate dehydrogenase level, and no or mild disseminated intravascular coagulation (DIC). Favorable prognostic factors for EFS were leukocyte counts < 10.0x10(9)/l, mild DIC, and no sepsis during induction therapy. In the JALSG APL97 study, we intensified chemotherapy for patients with leukocyte counts > or =3.0x10(9)/l, and are randomly testing whether further chemotherapy is required for APL patients with negative PCR for PML/retinoic acid receptor alpha in the maintenance phase.

[Infants 12 month-old or less as a high risk group in tuberculosis--comparison of clinical data with those in children aged one to two years].

A number of tuberculosis (TB) infants 12 month-old or less is larger than the ones of any other age groups with childhood TB in our hospital. This study was undertaken to elucidate clinically why infants 12 month-old or less suffered from TB most among infants and early children. We studied tuberculin skin reaction, isolation frequency of Mycobacterium tuberculosis (MTB) in gastric aspirates, and frequency of systemic dissemination of TB among 45 TB infants 12 month-old or less, and compared the results with those of 31 control TB infants and children aged 13 to 35 month-old. The frequency distribution of tuberculin skin reaction size among the studied infants was significantly smaller than that among the controls (p < 0.05). MTB was positive among 33 out of the 45 studied infants (73%) while 12 out of the 31 controls (39%), and the difference was significant (p < 0.005). Miliary TB and/or TB meningitis were seen among 8 out of the 45 studied infants (18%) while 1 out of the 31 controls (3%), and there was marginally significant difference between them (p = 0.054). These results suggest that delayed-type hypersensitivity and cell-mediated immunity to MTB among infants 12 month-old or less may be lower than those among infants and children aged 13 to 35 month-old, and the studied infants may be inferior in their capacity to kill mycobacteria and to encapsulate mycobacteria by granuloma formation.

Comparison of 3 surgical approaches to laparoscopic adrenalectomy: a nonrandomized, background matched analysis.

PURPOSE: To clarify the characteristics of surgical approaches to laparoscopic adrenalectomy we performed background matched analysis of clinical outcomes of the 3 approaches. MATERIALS AND METHODS: From February 1992 to July 2000 we performed 118 laparoscopic adrenalectomies in 115 patients with adrenal tumors. For these operations we used the anterior transperitoneal approach in 46 patients, the lateral transperitoneal approach in 32 and the lateral retroperitoneal approach in 40. RESULTS: To exclude the learning curve effect we eliminated our initial 20 patients treated with the anterior transperitoneal approach. To allow background matching of the 3 groups we also excluded 14 patients with tumors more than 5 cm., 6 who underwent conversion to open surgery and 1 patient who required 5 days of bed rest for retroperitoneal hematoma caused by bleeding from a trocar port. The final analysis included 16, 25 and 36 cases managed via the anterior transperitoneal, lateral transperitoneal and lateral retroperitoneal approach, respectively. Average operative time was significantly shorter for the lateral transperitoneal approach. Postoperative recovery was not significantly different in the lateral transperitoneal and lateral retroperitoneal groups. Postoperative complications included mild paralytic ileus in 2 patients and shoulder tip pain, probably peritoneal irritation due to carbon dioxide insufflation and bowel preparation, in 4 in the transperitoneal groups. Our results imply that the easiest procedure is the lateral transperitoneal approach but the lateral retroperitoneal approach is slightly less invasive. CONCLUSIONS: Although it is important to remember that this study was not a prospective randomized trial and, thus, had from certain biases, we believe that if a tumor is more than 5 cm. and/or the surgeon is not yet skilled in laparoscopic adrenalectomy, the lateral transperitoneal approach is the most suitable method. If the surgeon has performed at least 20 operations, the adrenal tumor is unilateral and the lesion is less than 5 cm., the lateral retroperitoneal approach seems to be more suitable because of its minimally invasive nature. The lateral retroperitoneal approach is also preferred in patients with a history of upper abdominal surgery. With improvements in technique and new instruments the time required for the lateral retroperitoneal approach has been significantly decreased.

Simultaneous bilateral laparoscopic adrenalectomy in ACTH-independent macronodular adrenal hyperplasia.

Laparoscopic surgery for urological conditions has now become popular worldwide. The case is reported of a 56-year-old woman who underwent simultaneous bilateral laparoscopic adrenalectomy for adrenocorticotropic hormone-independent macronodular adrenocortical hyperplasia (AIMAH), followed by autotransplantation of resected adrenal gland fragments. Simultaneous laparoscopic adrenalectomies seem feasible for a patient with AIMAH because of its minimally invasive nature. However, autotransplantation of adrenal fragments failed in this patient with AIMAH.

[A case of pheochromocytoma with von Recklinghausen's and review of 67 Japanese cases].

A 19-year-old woman with von Recklinghausen's disease was referred to our hospital because of right adrenal pheochromocytoma. The tumor was detected incidentally with the abdominal ultrasonography when she complained epigastralgia to the home doctor who treated her hypertension. Plasma and urinary catecholamines level were elevated. The tumor was removed by laparoscopy assisted adrenalectomy without pneumoperitoneum. The resected specimen was 35 x 60 x 75 mm in size and weighed 70 g. Pathological diagnosis was adrenomedullary pheochromocytoma. Postoperative course was uneventful. She has been well with no signs of recurrence after 7.5 years. We reviewed 67 Japanese patients previously reported as von Recklinghusen's disease with pheochromocytoma. Of the 60 patients whose details were described, 16.7% had metastases and pathological malignancy from pheochromocytoma.

Construction of Oka varicella vaccine expressing human immunodeficiency virus env antigen.

Oka varicella vaccine has been used to confer active immunity to varicella-zoster virus (VZV) in healthy and immunocompromised hosts. Based on its attenuated nature, Oka varicella vaccine expressing human immunodeficiency virus (HIV) env antigen was constructed by inserting the HIVenv gene into the viral genome and its immunogenicity was assessed in guinea pigs. The HIVenv gene encoding 296-463 amino acids was inserted between the sequences of the hepatitis B surface antigen and the thymidine kinase gene of the cloned plasmid and the recombinant virus was isolated by cotransfection of the chimeric plasmid with viral DNA. Insertion of the HIVenv gene into the viral genome was confirmed by PCR and sequencing of the viral genome of the recombinant virus. The recombinant virus expressed 30k HIVenv fusion protein in its infected cells. In guinea pigs, immunization with the recombinant virus induced an antibody response to both the HIV antigen and the V3 peptide of gp120 as well as VZV gE:gI. Cell-mediated immunity to the HIV antigen and gE:gI was assessed by the cutaneous reaction representing delayed type hypersensitivity. Immunized guinea pigs responded well to both the HIV antigen and gE:gI. Thus the recombinant Oka varicella vaccine expressing the HIVenv antigen induced both a humoral and cell-mediated immunity to the HIV antigen similar to VZV as Oka varicella vaccine induces humoral and cell-mediated immunity to VZV in the vaccinees. This recombinant Oka varicella vaccine expressing the HIVenv antigen may be evaluated for its immunogenicity as one of the AIDS vaccine candidates.

Aggressive neoplastic plasma cell growth with MLL gene rearrangement after high-dose therapy with autologous stem cell support for multiple myeloma.

We report a case of a patient with IgA kappa multiple myeloma (MM) mobilized with etoposide and subsequently receiving high-dose melphalan (HDM) with stem cell support. She relapsed rapidly post transplantation. Southern blot and fluorescent in situ hybridization analysis showed MLL gene rearrangement in the myeloma cells, which was not detected in the sample at diagnosis or in the PBSC harvested with etoposide plus G-CSF. These observations suggest that clonal rearrangement of the MLL gene is caused by etoposide. Patients with MM undergoing HDM with stem cell rescue may be at an increased risk of not only secondary leukemia, but also secondary genetic abnormalities in myeloma cells, especially those receiving priming with etoposide for peripheral blood stem cell collection.

Successful autologous peripheral blood stem cell transplantation for relapsed intravascular lymphomatosis.

We describe a case of relapsed intravascular lymphomatosis (IVL) successfully treated with autologous PBSCT. A 59-year-old Japanese female patient with IVL who had achieved CR after six courses of biweekly CHOP therapy developed lymphoma. She achieved a second CR after six courses of modified biweekly CHOP therapy, followed by autologous PBSCH and high-dose chemotherapy (CBDCA, VP-16, MCNU, CY) with PBSCT. There has not been any evidence of recurrence 48 months after PBSCT. Our case suggests that PBSC is acceptable as a source for stem cell rescue in IVL.

Potent cytolytic response by a CD8+ CTL clone to multiple peptides from the same protein in association with an allogeneic class I MHC molecule.

CTL clone 2C recognizes the allogeneic class I MHC molecule L(d) in association with peptides derived from alpha-ketoglutarate dehydrogenase (oxoglutarate dehydrogenase (OGDH)), a ubiquitous intracellular protein. One of these peptides, QLSPFPFDL (QL9), elicits more vigorous cytolytic responses than two previously identified naturally processed peptides with overlapping sequences, LSPFPFDL (p2Ca) and VAITRIEQLSPFPFDL (p2Cb), from OGDH. In this study, we show that QL9 forms a more stable complex with cell surface L(d) than does p2Ca or p2Cb and is processed from the longer, naturally occurring peptide p2Cb by 20S proteosomes in vitro. The N-terminal cyclized pyroglutaminyl QL9 (pyroQL9), a form of QL9 to which it is converted at the low pH used for peptide isolation from tissue extracts, is even more active than QL9 in cytotoxicity assays with 2C CTL. Overall, the results indicate that along with the abundant natural peptides p2Ca and p2Cb, the QL9 and other OGDH peptides of various lengths, sharing a conserved C-terminal sequence, are also processed and presented with L(d) as allogeneic ligands for T cells expressing 2C TCR. All these peptides, each available in a low amount, could act in concert at the cell surface, resulting in a high density of cognate ligands that accounts for the exceptionally potent cytolytic response by 2C CTL.

Clinical usefulness of chemotherapy based on an in vitro chemosensitivity test in urothelial cancer patients.

BACKGROUND: We evaluated the clinical usefulness of individualized chemotherapy based on an in vitro chemosensitivity test, i.e., the histoculture drug response assay (HDRA), for urothelial cancer. MATERIALS AND METHODS: 62 clinically obtained cancer specimens were studied. Each specimen was tested for sensitivity to nine anticancer drugs. The antitumor effect was calculated as the inhibition rate to their control values. The HDRA effective cytotoxic drugs were selected for clinical treatment. RESULTS: HDRA was possible in 58 out of 62 specimens (93.5%). Their chemosensitivity showed a wide variety even among the same histological category. No correlation was seen between histological grade and chemosensitivity. The effect of chemotherapy on the measurable lesions was studied in 12 patients and good clinical responses were obtained in 7 of them (58.3%). All 7 responders were the patients who received drugs predicted to be effective by HDRA. In 8 out of the 12 patients (66.7%), including 7 true-positive and 1 true-negative, HDRA correctly predlicted the clinical effect of chemotherapy. CONCLUSION: The HDRA might be feasible for predicting the efficacy and, therefore, selecting the proper anticancer drug for individual patients.

CD40 ligand immunotherapy in cancer: an efficient approach.

Cancer cells do not elicit a clinically sufficient anti-tumor immune response that results in tumor rejection. Recently, many investigators have been trying to enhance anti-tumor immunity and encouraging results have been reported. This review will discuss current anti-cancer immunotherapy; interleukin-2 therapy, tumor vaccine secreting Granulocyte macrophage-colony stimulating factor, dendritic cells fused with tumor cells, and CD40 ligand immunotherapy. Moreover, we introduce our two kinds of CD40 ligand immuno-genetherapy; (1) oral CD40 ligand gene therapy against lymphoma using attenuated Salmonella typhimurium (published in BLOOD 2000), (2) cancer vaccine transfected with CD40 ligand ex vivo for neuroblastoma (unpublished). Both approaches resulted in a high degree of protection against the tumor progression and they are simple and safe in the murine system.

Multicenter prospective study of interferon-alpha and conventional chemotherapy versus bone marrow transplantation for newly diagnosed patients with chronic myelogenous leukemia. Kouseisho Leukemia Study Group.

We compared interferon-alpha (IFN-alpha therapy with bone marrow transplantation (BMT) after initial conventional chemotherapy in patients with chronic myelogenous leukemia (CML) in a multicenter prospective study. Ninety patients with Philadelphia chromosome-positive CML in chronic phase were enrolled between 1991 and 1994. Sixty-six of 89 evaluable patients received IFN-alpha after conventional chemotherapy with hydroxyurea or busulfan (IFN-alpha group). Twenty-three patients received allogeneic BMT (BMT group). Fifteen of them received transplants from HLA-identical family donors and 8 from HLA-matched unrelated donors. Forty-seven of 66 patients (71%) in the IFN-alpha group and 17 of 23 patients (74%) in the BMT group achieved complete hematologic response, and 12% in the IFN-alpha group and 13% in the BMT group achieved partial hematologic response. Complete cytogenetic response was induced in 5 (8%), partial cytogenetic response in 8 (12%), and minor cytogenetic response in 12 (18%) in the IFN-alpha group. At a median follow-up of 54 months (range, 30-76 months), in the IFN-alpha group, the predicted 6-year survival rate was 54.5% and the predicted 6-year rate of those remaining in chronic phase was 45.7%. Compared with patients with no cytogenetic response, the patients with some cytogenetic response after IFN-alpha treatment had significantly superior survival and duration of the chronic phase even after correction for the time to response using landmark analysis (P < .05). In the BMT group, the predicted 5-year survival rate was 93.3% for family-donor BMT and 21.9% for unrelated-donor BMT Acute graft-versus-host disease of grade III or IV was observed in 1 of 15 patients who received family-donor BMT and 3 of 8 patients who received unrelated donor BMT. Prior treatment with conventional cytotoxic drugs induced early hematologic response and did not reduce the effect of IFN-alpha on CML. Unrelated-donor transplantation should be offered to some patients according to patient age, HLA-matching status, time from diagnosis to BMT, and risk factors.

[Treatment of acute promyelocytic leukemia with all-trans retinoic acid and chemotherapy--multicenter trial of the Japan Adult Leukemia Study Group (JALSG)].

We report herein the clinical results of a multicenter trial of the Japan Adult Leukemia Study Group for cases of newly diagnosed acute promyelocytic leukemia (APL) treated with all-trans retinoic acid and chemotherapy (JALSG AML-92 study). Of 196 evaluable patients, 173 (88%) achieved complete remission (CR). Multivariate analysis showed that no or minor purpura at diagnosis and age less than 30 years were favorable factors for achievement of CR. There was a significant difference in the 4-year event-free survival between the AML-92 study (54%) and both the AML-87 (32%) and AML-89 (32%) studies which consisted of intensive chemotherapy. Since prognosis in patients with APL largely depends on chemotherapy, it is important to consider more effective chemotherapy during induction and consolidation therapy.

Trisomy 10 in acute myeloid leukemia. Three additional cases from the database of the Japan Adult Leukemia Study Group (JALSG) AML-92 and AML-95.

To clarify the clinical and hematologic features of a rare numerical chromosome abnormality, we searched for trisomy 10 in acute myelogenous leukemias (AMLs) using the database of the Japan Adult Leukemia Study Group (JALSG) AML 92 and 95. Among the sequentially registered patients of JALSG-AML 92 (655 patients) and JALSG-AML 95 (531 patients), chromosome results were obtained in 1,074 patients (90.6%), and we found 3 patients with trisomy 10 as a sole abnormality. The first patient had an AML-M1 morphology with CD7 antigen; the patient obtained complete remission (CR) with the first course of chemotherapy. The second patient had an AML-M1 morphology without expressing CD7 antigen; this patient obtained CR, but relapsed 3 months later, and underwent allogeneic bone marrow transplantation. He suffered from chronic graft-versus-host disease and expired 38 months after the AML diagnosis. The third patient had AML-M0 with CD7 positivity. He obtained CR; however, brain abscess and cerebral hemorrhage occurred. In the literature, the mean age of patients with trisomy 10 AML is 57.8 years, the gender ratio is M/F = 1.5, and the frequency of M0/M1/M2 is 85.7%. A high incidence (81. 8%) of CD7 expression of leukemia cells is notable. About 73% of patients survived for greater than 12 months.