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Purpose: This study was done to evaluate the hemodynamic effects of a pumpless implantable extracorporeal membrane oxygenation (ECMO) circuit between the right ventricle (RV) and left atrium (LA) in a chronic canine model with an RV pressure overload., Method: We created a model of right-sided heart failure by pulmonary artery banding in ten dogs for a duration of more than 3 months. After demonstrating that the RV pressure increased, a bypass circuit was created between the RV and LA with an in-line oxygenator. Both the hemodynamics and gas exchange were measured., Results: The effects of a pulmonary bypass in nine dogs were studied. Approximately half of the RV output was passively shunted through the bypass circuit, and a marked reduction in the RV pressure and recovery from right heart failure were observed. After a complete ligation of the main pulmonary artery, five of the nine dogs survived more than 6 h. The RV pressure did not change significantly, but the cardiac output and blood pressure gradually decreased. The blood gas state was sufficiently maintained throughout the experiment., Conclusion: The present study indicates the hemodynamic benefit of a partial pumpless ECMO system in dogs with chronically pressure-overloaded right heart failure; however, the experimental preparation of the total pumpless ECMO circuit proved to be unstable.

Objective: To investigate the safety and feasibility of using mild hypothermia in neonates receiving extracorporeal membrane oxygenation (ECMO). Study design A prospective, nonrandomized pilot study of 25 neonates referred for ECMO. Whole body cooling was achieved by adjustment of the temperature of the extracorporeal circuit water bath. Five groups (N=5 per group) were each studied for the first 5 days of ECMO. The first group was maintained at 37 degrees C throughout the study period. Subsequent groups were cooled to 36 degrees C, to 35 degrees C, and, finally, to 34 degrees C, respectively, for 24 hours and the final group to 34 degrees C for 48 hours before being rewarmed to 37 degrees C. Patients were carefully assessed clinically and biologically. In addition to routine laboratory tests, cytokines (IL-6 and IL-8), complement (C3a), and molecular markers of coagulation (thrombin/antithrombin III [TAT], antithrombin III, and plasmin-alpha2plasminogen) were measured., Results: No major clinical or circuit problems were noted during cooling or rewarming. In particular, there were no problems of bleeding or cardiac arrhythmia. No significant difference was found between groups in terms of molecular markers of coagulation, complement, cytokines, and platelet transfusions., Conclusions: Applying mild hypothermia (34 degrees C) for 24 or 48 hours to neonates receiving ECMO is both feasible and safe.

To elucidate the mechanism of anti-inflammatory effect of partial liquid ventilation (PLV), cytokine concentration, surface CD11b, and macrophage expression were investigated in BALF. The 30-minutes group was treated with gas ventilation (GV) for 30 minutes after intratracheal LPS administration. The GV group was prepared in the same manner as the 30-minutes group, then the GV was continued for the following 2 hours. The PLV group was treated in the same manner as the 30-minutes group, and then received PLV with perflubron for the following 2 hours. Animals were euthanized to receive BAL. The PLV group showed a tendency to have a higher concentration than the GV group of TNF-alpha, MIP-2, and CINC-1 as measured by ELISA, although there were no significant differences. The ratio of expressions of CD11b and macrophages to total leukocytes were determined by flow-cytometry. There were no significant differences in the ratio of CD11b-positive expression to acquired cells (GV: 63.6 +/- 8.4%, PLV: 60.5+/-5.4%, P=0.73). However, the proportion of macrophages was significantly increased (GV: 5.6 +/-1.5, PLV: 14.0+/-1.3, P=0.006). These results suggest that the anti-inflammatory effect of PLV is not caused by the change in CD11b expression, and that PLV affects the proportion of macrophage among BALF cells.

Three cases of pulmonary mucoepidermoid carcinoma, which were surgically treated in our hospital, were reported. The first case was 28-year-old male, who had hemoptysis, underwent right upper lobectomy and mediastinal lymph node dissection on October 31, 1973. The tumor located and obstructed the ostium of right B2. The diameter was 2.3 x 1.8 cm. The second case was 63-year-old male, who had obstructive pneumonia, underwent left upper lobectomy and mediastinal lymph node dissection on November 18, 1998. The tumor located and obstructed the ostium of lingular bronchus, and the diameter was 1.8 x 1.2 cm. The third case was 25-year-old male, who had obstructive pneumonia, underwent left sleeve lower lobectomy and mediastinal lymph node dissection on May 26, 1999. The tumor located in ostium of left B6, and it obstructed lower bronchus and expanded into the lung. The diameter was 4 x 2 cm. All cases were diagnosed as low grade malignancy with no lymph node metastasis. The first case survived without recurrence at least 5 years as far as we followed, and the others are surviving until now without any signs of recurrence. These three cases were 0.19% of total resected lung cancers in our hospital from 1969 to 1999.

Lung rest is the primary goal of venovenous extracorporeal membrane oxygenation for severe acute respiratory failure. To achieve this there has to be adequate extracorporeal flow. This can be achieved by a two-cannula technique in most cases. In some cases, extra flow is either not achievable or causes excessive recirculation. We report 8 patients in whom we achieved adequate blood and oxygen delivery using a three-cannula technique. Five patients survived (62.5%).

Blood flow is believed to affect the thrombogenicity of extracorporeal circulation (ECC). The purpose of this study was to look at the relationship between blood flow and thrombogenicity in a rabbit model of ECC. Rabbits were anesthetized and systematically heparinized. Bilateral jugular cannulation was performed, and the animals were placed on venovenous ECC. The circuits were composed of 1 m of 1/4 inch size surgical grade polyvinylchloride (PVC) tubing. ECC was maintained for 4 hours. Three experimental groups were studied: a high flow group (n=7; flow rate: 30 ml/min/Kg), low flow group (n=7; flow rate: 10 ml/mg/Kg), and no ECC group (n=7). Platelet count, fibrinogen concentration, PaO2/FiO2, and postmortem findings were evaluated. Platelet consumption was higher with high flow, and fibrinogen consumption was higher with low flow.

Objective: Tracheal reconstruction is necessary in patients with extensive tracheal stenosis caused by neoplasm, trauma, and congenital disease. We investigated the possibility of tracheal allotransplantation with cryopreserved grafts in a canine model., Methods: A seven-ring section of thoracic trachea was removed in 19 adult mongrel dogs. In group A (n = 4), a five-ring tracheal autograft was implanted. In group B (n = 6), a five-ring allograft was implanted without immunosuppression. In group C (n = 9), a five-ring cryopreserved tracheal allograft was implanted without immunosuppression. Omentopexy wrapping around the grafts and both anastomotic sites was used in all animals., Results: All grafts survived without any evidence of atrophy or stenosis in group A. All animals in group B died of severe airway obstruction within 1 month, and postmortem examination of these grafts showed epithelial defect and necrotic tracheal cartilage in the scar tissue. In group C, no animals died of asphyxia caused by severe stenosis of the grafts. The graft epithelium was no longer present 20 days after transplantation, and the graft was covered with regenerated epithelium within about 60 days after the operation., Conclusion: These findings show that cryopreserved tracheal allografts can be transplanted by means of omentopexy without immunosuppression and that cryopreservation may reduce tracheal allogenicity.

To study the effect of partial liquid ventilation (PLV) with perfluorocarbon on acute respiratory failure, 3 groups of 17 rabbits were examined to compare. After acute respiratory failure was induced by lung lavage with sea water in 12 of the 17 rabbits, 7 of the 12 rabbits were treated with conventional mechanical ventilation (AC group) and 5 of the 12 rabbits were treated with PLV using perfluorocarbon (AP group). The remaining 5 normal rabbits without acute respiratory failure were treated with PLV with perfluorocarbon as a control group (PL group). In the PL group, PaO2, PaCO2, blood pH, pulmonary compliance or pathological findings were not so changed after PLV. In the AC and AP groups, PaCO2 significantly increased, and in contrast, PaO2 and pulmonary compliance significantly decreased after lung lavage. However, these findings improved to almost the same levels as those of a control group within 2 h after the PLV treatment in the AP group, but in the AC group, these gradually deteriorated over time. As for the pathological findings, pulmonary vascular congestion, alveolar hemorrhage and inflammatory infiltration were observed in the AC group. However, these findings were not observed in the specimens of the AP group. From these results, PLV with perfluorocarbon was shown to be useful to improve gas exchange and pulmonary functions without major side effects.

In this study, we investigated whether the regenerated epithelia were recipient phenotype or donor phenotype using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method. Preoperatively 24 mongrel dogs were classified to 14 types by PCR-RFLP result from peripheral blood. The PCR-RFLP result of peripheral blood agreed to that of recipient epithelia. The cryopreserved tracheal allotransplantation was performed among the five pairs in which we could distinguish donor from recipient by PCR-RFLP. The epithelia of graft at 10 days after transplantation showed donor phenotype, but the epithelia at postoperative 20 days or more showed recipient phenotype. These results showed that allogenic epithelium remained in early post-transplant time and was gradually omitted. The epithelia migrated gradually from the anastomotic site, and the graft was covered with regenerated epithelia showing recipient phenotype within about 50 post-transplant days.

Extracorporeal membrane oxygenation (ECMO) for respiratory failure was reviewed. ECMO progressed from laboratory research to initial clinical trials in 1972. Following a decade of clinical research, ECMO is now standard treatment for neonatal respiratory failure refractory to conventional pulmonary support techniques worldwide. The application of neonatal ECMO has been extended with improved outcome to premature and low birth weight infants as well as older children and adults. As of July 1994, 9,258 neonates, 754 pediatric, and 130 adult patients with respiratory failure treated with ECMO were entered in the registry of the Extracorporeal Life Support Organization (ELSO). Overall survival rates were 81% in neonates, 49% in pediatric, and 38% in adult patients. Recently the adult and pediatric populations treated with ECMO have increased rapidly, and the outcome has improved significantly.

In February, 1990, a 49-year-old man was admitted with petechia and gingival bleeding. The peripheral blood showed 5,200 leukocytes/microliters including 73% abnormal promyelocytes and 24,000/microliters platelets. Bone marrow puncture revealed that nucleated cell count was 331,250/microliters including 85.4% abnormal promyelocytes with 46XY, i(17q) chromosome. Coagulation tests revealed DIC. He was diagnosed as having acute promyelocytic leukemia, and he was treated with the BHAC-DMP protocol. He achieved complete remission, and received consolidation therapy and maintenance therapy. However, he relapsed in May, 1991 with 46XY, 16q-, i (17q) chromosome. He was treated with BHAC-MV protocol and again achieved complete remission. In June, 1992, he re-relapsed and 3.6% blasts and 10% abnormal promyelocytes was found in his bone marrow. He was treated for 14 days with 15 mg Aclarubicin without any change. Then he was treated with 60 mg All-trans retinoic acid (ATRA). After administration of ATRA, his peripheral blood leukocyte count increased temporarily but bone marrow suppression continued. Then he received continuous subcutaneous infusion of 24 micrograms/day granulocyte colony-stimulating factor (rhG-CSF). After treatment with ATRA and rhG-CSF, he entered a third complete remission.

Extracorporeal Membrane Oxygenation (ECMO) has been adopted as a means of strong respiratory support. In lung transplantation, reimplantation response is still a serious problem. It causes severe respiratory failure which is refractory to mechanical ventilation in some cases. The purpose of this study was to evaluate the effects of veno-venous ECMO after lung transplantation using a canine autotransplantation model. The autotransplantation model was created by keeping the left lung in a warm ischemic state for 2 h. After reperfusion, the right pulmonary artery was ligated. The following two groups were studied: Group 1, Control group, (no ECMO group) (n = 6). After reperfusion, both lungs were ventilated without ECMO. Group 2, ECMO group (n = 7). After reperfusion, veno-venous ECMO support was introduced with reduction of mechanical ventilation. In the no ECMO group, four of the animals died within 210 min after reperfusion. In the ECMO group, two of the animals died of severe pulmonary edema. Data of blood gas analyses (PaO2, PaCO2, and SvO2) after reperfusion were significantly better in the ECMO group, whereas there were no significant differences in both shunt fraction and pulmonary vascular resistance index. In this model with severe pulmonary edema induced by warm ischemia, veno-venous ECMO contributed to the improvement of hypoxemia and hypercapnia, but did not improve pulmonary hemodynamics.

A clinical study was conducted of 17 patients aged less than 40 years who received resection for lung cancer in our department. The 17 cases made up 1.8% of the total series of 924 resected lung cancer cases, with the number of cases increasing as the age of 40 years was approached. The male-female ratio was 1.1:1, with proportion of women higher than in the total series of lung cancer cases. The histological type of included a high proportion of adenocarcinomas (47.0%), while squamous cell carcinomas were few. In addition, the proportion of tumors of low-grade malignancy such as carcinoid tumors and mucoepidermoid carcinomas was high. The majority (58.8%) of cases were detected by mass screening. As a result, the number of stage I cases was high (10 cases, 58.8%), and curative resection could be performed in 70.8%. The prognosis of these young patients did not differ significantly from that of the total resected group, with a 5-year survival rate of 62.4% achieved. It was considered that the prognosis of lung cancer in young persons can also be improved with early detection by mass screening and active surgical intervention.

Twenty-two patients with steroid-unresponsive idiopathic thrombocytopenic purpura (ITP) were treated with cepharanthin, biscoclaurin alkaloid. Cepharanthin was administered orally at a daily dose of 40 mg. Continuous elevation of platelet counts of 6.6-15.0 x 10(4)/microliters and 3-5 x 10(4)/microliters was attained in five and two patients, respectively, 1 to 4 months after the administration. Treatment with cepharanthin might be worth attempting in refractory ITP.

Myelodysplastic syndromes that occurred in two young brothers are reported. A 19-year-old man was admitted to Kobe City General Hospital in May 1990 because of fever and nasal bleeding. On admission his hemoglobin was 5.5 g/dl, platelet count 1.5 x 10(4)/microliters and white cell count 1,700/microliters with 18% neutrophils and 80% lymphocytes. Bone marrow aspirate showed dysplastic features of trilineage blood cells with 4.8% myeloblasts. A diagnosis of refractory anemia was made. His younger brother, a 17-year-old man was examined in May 1990 because of increasing fatigability of 2 years' duration. His hemoglobin was 8.7 g/dl, platelet count 2.1 x 10(4)/microliters and white cell count 2,800/microliters. Bone marrow aspirate revealed morphological abnormalities in three lineages with 5.2% myeloblasts. He was diagnosed as having refractory anemia with excess of blasts. Their parent are consanguineous. The onset at a young age, reduced CD4 lymphocytes and similarity of dyshematopoietic findings suggests the presence of common genetic disorder in the pluripotent hematopoietic stem cells.

The efficacy of traditional Chinese medicine (Kampo medicine) was examined in 40 patients with steroid-unresponsive idiopathic thrombocytopenic purpura (ITP). All patients were, at first, given Hochuekihi-to, and when they were refractory, therapy was switched to Sairei-to, Ninjinyoei-to, and Kamikihi-to. The efficacy rate was 20.0% by Hochuekihi-to, 20.7% by Sairei-to, 5.5% by Ninjinyoei-to and 6.7% by Kamikihi-to, respectively. Thus, overall responders were 12 in 40 patients with an effective rate of 30.0%. The mechanism of action of traditional Chinese medicine is discussed in relation to the production of various kinds of cytokines.

A 70-year-old male was admitted with complaints of anterior chest pain and tumor formation. He has a history of pulmonary tuberculosis and was performed artificial pneumothorax therapy 37 years ago. The diagnosis on admission was perforation of empyema cavity into the chest wall. But thoracotomy revealed that the chest tumor arising from chronic empyema wall was a malignant lymphoma. Decortication and extirpation of the tumor were performed with combined partial resection of chest wall. Immunohistological examination showed that the histology was diffuse large T cell type of Non-Hodgkin's malignant lymphoma. The patient has been alive and well for 24 months postoperatively.

We examined whether recombinant cytokines enhance the in vitro platelet production of interleukin-3 (IL-3)-induced human megakaryocytic colonies (Meg-colony). We classified Meg-colonies into four categories based on platelet production during in situ observation on day 14: type 0, absence of cytoplasmic processes in a colony; type 1, one to three processes in at least one megakaryocyte in a colony; type 2, four to eight processes; type 3, more than nine processes or division of cytoplasm. Type 3 colonies were considered to be platelet-producing. In control cultures, type 1 Meg-colonies were dominant, followed by type 2, type 3 and type 0. Of the cytokines added at the initiation of culture, interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6), and granulocyte/macrophage colony stimulating factor (GM-CSF) significantly increased the number of colonies. Furthermore, these three cytokines significantly elevated the proportion of type 3 colonies. Interleukin-4 (IL-4), granulocyte-CSF, macrophage-CSF and erythropoietin did not affect the colony count or distribution of colony type. IL-1 alpha, IL-6 and GM-CSF also significantly elevated the proportion of type 3 colonies, even when added to the culture on days 8 or 11. These results indicate that IL-1 alpha, IL-6 and GM-CSF promote platelet production of in vitro Meg-colonies.

Four human myeloma cell lines (MM-S1, MM-A1, MM-Y1 and MM-C1) were established from patients in the terminal stage of multiple myeloma. All the cell lines were PCA-1 positive and three were CD38 (OKT10) positive. The class of cytoplasmic immunoglobulin in each of these cell lines was identical to that of the monoclonal protein detected in each patient. Epstein-Barr virus nuclear antigen was negative in all cell lines. An examination of the tritiated thymidine uptake showed that all four cell lines proliferated in response to interleukin-6 (IL-6), while MM-S1 also responded to IL-5. Immunological staining with an anti-IL-6 receptor monoclonal antibody revealed the presence of receptors for IL-6 on the cells from each cell line. Three of them formed colonies dependent on IL-6 in methylcellulose semi-solid culture. All four cell lines grew better when human plasma was added as a supplement to the culture in comparison to fetal calf serum. Northern blot analysis showed that the three cell lines tested did not express IL-6 messenger RNA. These results indicate that these four cell lines are responsive to IL-6, but not by an autocrine mechanism, at least in the three lines examined.

We examined in vitro growth pattern of myeloma cells from 21 patients with multiple myeloma either in liquid suspension or methylcellulose semi-solid culture, both in the presence of interleukin-6 (IL-6). The survival or growth of myeloma cells in liquid culture was classified into four categories. Type 1: myeloma cells survived for only 2-3 weeks in eight patients; Type 2: survival for 1-2 months in seven patients; Type 3: survival for more than 3 months without an obvious increase in cell number in three patients; and Type 4: continuous proliferation (cell line) in three patients. As the clinical stage advanced, the survival of myeloma cells became longer. All three myeloma cell lines were obtained from patients in an advanced clinical stage. Human plasma added to the liquid culture induced the survival or growth of myeloma cells better than fetal calf serum in any survival or growth type. Myeloma colonies or clusters were generated in seven of 21 patients, though myeloma colony formation was restricted to Type 4 patients. IL-6 neither prolonged the survival of myeloma cells nor promoted their growth in vitro except for Type 4 cells. Moreover, IL-6 did not increase the success rate of generating myeloma colonies in vitro. However, IL-6 did elevate the number of myeloma clusters in Types 1, 2 and 3 patients examined. These results suggest that IL-6 has a minor proliferative effect on myeloma cells in semi-solid culture but not in liquid suspension culture except for cells from patients with aggressive myeloma.

1,25-Dihydroxyvitamin D-3 (1,25(OH)2D3) suppresses colony formation of normal human granulocyte macrophage progenitors (CFU-GM) and induces differentiation of colonies into monocyte macrophages in vitro. We examined whether or not the target cell of 1,25(OH)2D3 is only CFU-GM in the suppression and differentiation of colonies by the agent. Reduction of colony counts was observed only when 1,25(OH)2D3 was added to CFU-GM cultures at days 0 or 3, and after day 5 the agent did not affect the colony count. However, the delayed addition of 1,25(OH)2D3 elevated the proportion of granulocyte macrophage (GM) or macrophage (M) colonies even after 5 days of culture. We confirmed transformation of day 11 colony cells into macrophages by 1,25(OH)2D3 during the following 3 days' culture period based on serial observations of single colonies. Day 11 colonies contained very few CFU-GM and their most immature cells were promyelocytes. Short-term exposure to 1,25(OH)2D3 (4 h) of bone marrow cells, which had been precultured for 24 to 72 h with a purified granulocyte-colony stimulating factor caused a reduction of colony counts but did not elevate the proportions of GM or M colonies. These results indicate that 1,25(OH)2D3 inhibits the growth of CFU-GM itself and induces differentiation into macrophages at the progeny level (probably promyelocytes) and not at the level of CFU-GM.

We demonstrated the expression of the erythropoietin (EPO) receptor by a human myeloma cell line (MM-S1) which was established in our laboratory. EPO dose-dependently stimulated the proliferation of MM-S1 cells. Binding of radioiodinated EPO (125I-Epo) to MM-S1 cells was competitively inhibited by unlabeled EPO, but not by other recombinant cytokines. Specific binding of 125I-Epo to MM-S1 cells was saturable, and the Scatchard analysis revealed 330 EPO binding sites per cell with a Kd of 0.56 nmol/L. Bound EPO was internalized by MM-S1 cells during incubation at 37 degrees C. This is the first report describing the expression of the EPO receptor by human cells other than those of the erythroid lineage.

We performed wide resection of recurrent carcinoid tumor of thymus. A 62-year-old male patient admitted to our department because of swelling of anterior chest wall. He had received extirpation of thymic carcinoid tumor 5 years ago and he was pointed out large mass formation in anterior mediastinum before admission. Wide resection of tumor including pericardium, chest wall, left lung and left brachiocephalic vein was performed. Left brachiocephalic vein was reconstructed and pericardium was replaced with Gore-Tex patch. The carcinoid tumor of thymus sometimes invade to adjacent organs and is apt to recur long time after first operation.

We tried to treat 13 patients with myelodysplastic syndromes (MDS), leukemias and myeloproliferative disorders, with alfacalcidol for their hematological improvement. Eight of them had MDS, 2 acute leukemia (M3, M4), 1 chronic myelogenous leukemia and 2 primary myelofibrosis. All patients were untreated except for 3 patients (PASA, RAEB, AML-M4) who had been treated with mepitiostane, prednisolone and BH.AC-AMP regimen, respectively, prior to alfacalcidol therapy. All patients received alfacalcidol orally for at least one month. The dosage of alfacalcidol ranged from 0.25 to 10 micrograms/day, and the medicine was administrated intermittently when the dosage exceeded 6 micrograms/day to prevent hypercalcemia. The therapeutic effectiveness of alfacalcidol was evaluated according to a criteria by Koeffler (Cancer Treat Rep 69: 1399, 1985) with minor modifications. Three patients (PASA, RAEB, CMML) showed partial response, 3 (RAEB, RAEB in T, AML-M4) minor response and rest of the patients did not respond. The hematological improvement of 6 responders was transient (from 1 to 2 months), however, one patient (PASA) is still responding to alfacalcidol therapy (0.25 microgram/day) for over 12 months. The dysplastic features of hemopoietic cells in the bone marrow showed no noticeable change during the hematological improvement in these responders, suggesting the improvement was obtained as a result of alteration in the proliferation or differentiation of neoplastic clone. None of 13 patients developed hypercalcemia. One patient (AML-M4) became excitable on high dose alfacalcidol (10 micrograms/day). In conclusion, alfacalcidol therapy is effective in some patients with MDS or leukemias and appears worthy especially in the clinical state in which chemotherapy is not indicated.

A new cell line of human erythroleukemia cells differentiates spontaneously so that 30% of the cells are always hemoglobinized. Erythropoietin did not affect the percentage of such cells but stimulated the cell growth, indicating that the cells have functioning receptors. Binding of human recombinant radioiodinated erythropoietin to the receptors was specific. The bound ligand was internalized into cells at 37 degrees C but not at 15 degrees C. Scatchard analysis showed two classes of binding sites. Covalent binding of erythropoietin to its receptors yielded two products detected on sodium dodecyl sulfate-polyacrylamide gels electrophoresed under reducing conditions. Under non-reducing conditions, these species disappeared and larger products appeared.

We grew multilineage hemopoietic colonies in vitro from 4 patients with myeloproliferative disorders (MPD) having chromosomal aberration, and performed cytogenetic analysis of single CFU-GEMM, BFU-E and CFU-C-derived colonies on Day 14 of culture. In Patient 1 with acute myelofibrosis, CFU-GEMM and BFU-E colonies had only a 47, XX, +C karyotype. In Patient 2 with polycythemia vera, CFU-GEMM, BFU-E and CFU-C colonies all showed the same abnormal karyotype of 46, XY, -12, +der(12)t(1;12). Patients 3 and 4 had primary myelofibrosis, and their respective karyotypes were 46, XY, 13q- and 46, XX, -6, +der(6)t(1;6) in CFU-GEMM, BFU-E and CFU-C colonies. In these 4 patients, the karyotype of bone marrow or circulating mononuclear cells was identical to that of hemopoietic colonies. These results indicate a clonal origin of MPD at the level of CFU-GEMM.

A 71-year-old female was diagnosed as hypoplastic leukemia (ALL, L 2). Vitamin D3 (D3) therapy with alfacalcidol was successful and remission continued for approximately 4 months. However, the leukemia became refractory to D3, and low dose Ara-C combined with D3 was ineffective. Combined chemotherapy with vincristine, cyclophosphamide, L-asparaginase and prednisolone, low dose aclarubicin, OK-432 and etretinate ended in a failure. Treatment with mepitiostane was started and 1 month later obvious elevation of hemoglobin concentration, white cell and platelet count was observed. A bone marrow aspirate showed distinct recovery of normal hemopoiesis without residual leukemic cells. The patient has been staying in the complete remission for over 15 months with mepitiostane therapy (30 mg, daily). Androgen therapy, such as mepitiostane, appears to be effective in some patients with hypoplastic leukemia which does not indicate intensive chemotherapy.