Dose-reduced conditioning regimen followed by allogeneic stem cell transplantation in patients with myelofibrosis with myeloid metaplasia

Three patients with myelofibrosis received allogeneic stem cell transplantation after a dose-reduced conditioning regimen of busulphan (8 mg/kg), fludarabine (180 mg/m2) and antithymocyte globulin (4 x 10 mg/kg). The median age at transplantation was 51 years (range 44-58). All patients engrafted with a leucocyte count > 1.0 x 10(9)/l after a median of 18 d (range 16-20). Grade II acute skin graft-versus-host disease (GvHD) occurred in one patient. One limited and one extensive chronic GvHD was observed. All patients achieved complete haematological remission. In one patient the fibrosis resolved completely 180 d post transplant. All patients are alive 126, 466 and 764 d after transplantation.     

沙利度胺联合干扰素α-2b治疗原发性骨髓纤维化疗效观察

目的：观察沙利度胺联合干扰素2b治疗原发性骨髓纤维化（IMF）的疗效。方法：IMF患者9例,口服沙利度胺100-250mg／d,分2～3次口服。干扰素α-2b300万U／次,皮下注射,3次／周,治疗3个月以上。根据治疗前后白细胞计数、血红蛋白测定、血小板计数、脾脏大小的变化、腹胀的改善及骨髓活检来评定疗效。结果：9例脾肿大患者均明显缩小,其中4例巨脾患者缩小更显著;5例白细胞升高患者,3例恢复正常,2例明显降低;4例轻中度贫血患者2例恢复正常,2例有所上升;3例血小板升高患者,均恢复正常;6例腹胀患者,4例消失,2例明显减轻;复查骨髓活检（髂后）,9例IMF患者治疗前后骨髓纤维化无明显进展。结论：沙利度胺联合干扰素α-2b是治疗IMF的有效方法之一。     

Acute megakaryoblastic leukaemia: a prospective study of its identification and treatment

Acute megakaryoblastic leukaemia remains an uncommonly recognized disorder, usually identified by electron microscopy or with monoclonal antibodies. Using two monoclonal antibodies (HP1-1D identifying glycoprotein IIB/IIIA and W1-23 identifying von Willebrand factor) we have studied during a 12 month period all cases of acute leukaemia with FABL2,M1 or undifferentiated morphology presenting in our cooperative group 'Grupo de Hematólogos de Puebla' in México. Six of 21 FAB L2, M1 or undifferentiated leukaemias were classified immunologically as megakaryoblastic. Five of these patients had myelofibrosis and two had normal platelet counts but abnormal platelet aggregation function. All six patients were treated with low-dose cytosine arabinoside (10 mg/m2) administered subcutaneously, twice daily in 21 d courses). Haematologic response was achieved in five cases while the sixth died before completing one course. Three patients relapsed within the first month after completing the chemotherapy and died. Two patients remain in remission 11 and 15 months after initial treatment. It is our impression that the prevalence of acute megakaryoblastic leukaemia has been under-estimated, and that low-dose cytosine arabinoside treatment may be of value in its management.     

Pulmonary Inflammation of Well-Dispersed Multi-Wall Carbon Nanotubes Following Intratracheal Instillation: Toxicity by Fiber of 1–5 μm in Length

The pulmonary toxicity of multi-wall carbon nanotubes (MWCNT) were examined by intratracheal instillation. We prepared a well-dispersed MWCNT dispersion including MWCNTs of 3.71 µm geometric average length. The fiber length of most of the MWCNTs in the dispersion was 10 µm or less. The MWCNT dispersion was administered to rat lung by single intratracheal instillation at doses of 0.2 mg and 0.6 mg/rat. Bronchoalveolar lavage fluid (BALF) was collected at 3 days, 1 week, 1 month, 3 months, and 6 months after instillation. The influences of the longer MWCNTs on the induction of inflammation and oxidative stress were examined by the number of neutrophils, cytokine induced neutrophil chemoattractant-1 (CINC-1), CINC-2, CINC-3 and HO-1 in the BALF. Additionally, ho-1 gene expression in the lung was examined. The intratracheal instillation of MWCNT induced transient inflammation dose dependently in the lung. The number of neutrophils was highest at 3 days after instillation and then decreased. However, the neutrophils in the MWCNT administered animals tended to be higher than in the control group until 3 months after instillation. The CINC-1 and CINC-2 concentrations in the BALF increased at 1 month after instillation. There were no significant differences in CINC-3 and HO-1 between the MWCNT administered animals and the control animals. These results revealed that the MWCNTs of 1–10 µm in length induced persistent inflammation in rat lung. There were no remarkable differences between the MWCNTs in the present study and previously reported, shorter MWCNTs prepared from “the same” raw MWCNT material.     

Long-term results of the UHKT-911 study of adult patients under 65 years of age with de novo acute myeloid leukemias without favorable karyotypes

Between February 1991 and April 1994 induction chemotherapy of 32 adult consecutive patients under 65 years with de novo acute myeloid leukemias (AML) was started in the study UHKT-911. They were 19 women and 13 men, aged 18-63 (median 44) years. Their AML were classified according to the FAB classification: 3 M0, 3 M1, 9 M2, 14 M4, 3 M5. Induction chemotherapy consisted of 1-2 cycles with 3-4 doses of daunorubicin (DNR) 45 mg/m2/d i.v. and 14 doses of cytosine arabinoside (Ara-C) 200 mg/m2 per 3-h infusion every 12 hours. After the treatment patients, not being in complete remission, got the HD cycle with 10 high-doses of Ara-C 2000 mg/m2 per 3-h infusion every 12 hours i.v. and DNR 45 mg/m2/d i.v. on days 4 and 5, then the EMi cycle composed of etoposide 100 mg/m2/d i.v. for 5 days and mitozantrone 10-12 mg/m2/d i.v. on days 1, 3 and 5. Complete remission (CR) was achieved in 25 of 32 (78%) patients after 1-3 cycles. Five patients died between days 5 and 24 of treatment of infections, two patients were resistant to 4 cycles of induction therapy and survived 8.4 and 13.5 months. Three patients chose allogeneic bone marrow transplantation in their 1st CR from their relatives. Two of them have been living in CR for 115 a 110 months since diagnosis, the third died of sepsis on the day 52 after transplantation. Two patients in CR died of infections after their 2nd. consolidation cycle. Twenty patients in CR completed 2-4 consolidation cycles (1-3 HD, 1 EMi). Median of their CR duration was 17.8 (2-117) months. Relapse appeared in 12 cases after 4.4-34.8 (median 12.5) months, 8 patients (6 women and 2 men, aged 29-63 years) have remained longer than 5 years in their 1st. CR. Cytogenetic examination of their bone marrow showed a normal karyotype in 4 cases, 1x 46,XX,del(1)(p32p34), 1x 46,XX,16p+, 1x 47,XX,+mar, 1x 46,XX,del(5)(q22q33). After 62 months in CR a pancytopenia with dysplastic bone marrow changes developed in one of them, probably a secondary myelodysplastic syndrome, lasting for further 33 months. Event-free survival at 5 years was 27.5% (8/29 patients), significantly better (p = 0.046) against 7.5% (3/40) patients treated without HD cycles in the years 1982-1987. The same difference was observed in 7.5-year overall survival (p = 0.036) between the two studies, when 3 of 6 patients 60-64 years old remain in their 1. CR.     

The role of transforming growth factor-β in PEG-rHuMGDF-induced reversible myelofibrosis in rats

Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) injected at a suprapharmacologic dose (100 μg/kg) daily for 5 d in normal rats caused marked increases in marrow megakaryocytes and platelet counts at 6–8 d followed by gradual decreases to control levels at 10–20 d. Interestingly, in addition to the expected thrombopoiesis, PEG-rHuMGDF was associated with myelofibrosis with a predominance of reticulin fibres at day 10 followed by complete normalization by day 20. At 6–8 d, the levels of transforming growth factor-β1 (TGF-β1) in the extracellular fluid of the marrow, the platelet poor plasma, and the platelet extract were increased 23-, 7- and 2-fold, respectively. The elevated levels of TGF-β1 were gradually reduced to baseline levels at 13–20 d in accordance with the normalization of myelofibrosis and thrombopoiesis. An ultrastructural analysis showed that large fragments of megakaryocytes were deposited in the marrow parenchyma of PEG-rHuMGDF-treated rats at day 6. PEG-rHuMGDF administration at pharmacologic doses (1 and 10 μg/kg) did not induce the deposition of reticulin fibres in the marrow. These findings suggest that TGF-β1 leaked from megakaryocytes is involved in the development of the PEG-rHuMGDF-induced myelofibrosis and that this is a reversible process related to the regulation of the excess production of platelets.     

Long-term effects of distal splenorenal shunt with splenopancreatic and gastric disconnection on hypersplenism due to liver cirrhosis

BACKGROUND/AIMS: Though the distal splenorenal shunt has been applied for gastroesophageal varices caused by liver cirrhosis, many patients develop secondary hypersplenism due to the portal hypertension following liver cirrhosis. We examined whether this operation could be effective for alleviating secondary hypersplenism for a long post-operative period. The subjects were 42 cases with gastroesophageal varices following liver cirrhosis in which we had performed distal splenorenal shunts with splenopancreatic and gastric disconnection at our institution in the period from 1983 1994 and the post-operative survival periods had been over 3 years. METHODOLOGY: White blood cell counts, platelet counts and spleen volume were measured prior to operation, 1 month after operation and during the post-operative period of 3-5 years. Quality of life and clinical symptoms were evaluated during the post-operative period of 3-5 years. RESULTS: White blood cell counts, platelet counts and spleen volume were improved respectively at 1 month and during the 3-5-year period after surgery, compared to those prior to operation. None of the clinical symptoms of hypersplenism were observed and the long-term performance status was satisfactory. CONCLUSIONS: We can conclude that the distal splenorenal shunt with splenopancreatic and gastric disconnection alleviated hypersplenism for post-operatively long periods.     

Efficacy of pipobroman in the treatment of polycythemia vera: long-term results in 163 patients

BACKGROUND AND OBJECTIVES. Polycythemia vera (PV) is a myeloproliferative disorder, characterized by the expansion of the red cell mass. Our purpose was to evaluate the efficacy of pipobroman (PB) in the long-term control of PV and to assess early and late events. DESIGN AND METHODS. From June 1975 to December 1997, 163 untreated patients with PV (median age 57 years, range 30-82) were treated with PB in a single Institute for a median follow-up of 120 months. The diagnosis was made according to the Polycythemia Vera Study Group criteria. PB was given at the dose of 1 mg/kg/day until hematologic response (hematocrit < 45% and platelets < 400x109/L) and of 0.3-0.6 mg/kg/day as maintenance therapy. RESULTS. Hematologic remission was achieved in 94% of patients in a median time of 13 weeks (range 6-48). Median overall survival was 215 months, with a standardized mortality ratio of 1.7. The cumulative risk of death was 11%, 22%, and 26% at 7, 10, and 12 years, respectively. The incidence of thrombotic events was 18.4x105 person-year and the cumulative risk was 6%, 11%, 16%, and 20% at 3, 7, 10, and 12 years respectively. Acute leukemia occurred in 11 patients, myelofibrosis in 7, and solid tumors in 11. The 10-year cumulative risk of leukemia, myelofibrosis, and solid tumors was 5%, 4%, and 8%, respectively. In the logistic analysis age over 65 (p = 0.0001) and thrombotic events at diagnosis (p = 0.001) were significantly correlated with a higher risk of death. Female gender (p = 0.02) and age over 65 (p = 0.01) significantly influenced the occurrence of thrombotic complications. Age was the only significant risk factor for leukemia (p = 0.04) and for solid tumors (p = 0.03), while the duration of PB treatment did not influence these risks. No significant risk factor was demonstrated for myelofibrosis. INTERPRETATION AND CONCLUSIONS. This study demonstrates in a large series of patients, observed for a long period, that pipobroman is effective in the long-term control of PV. The risk of early thrombotic complications at 3 years is 6% and the 10-year risk of acute leukemia, late myelofibrosis, and solid tumors is 5%, 4%, and 8%, respectively. The duration of pipobroman treatment did not correlate with these events.     

Beneficial treatment with methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside in a patient with primary myelofibrosis

We attempted treatment with methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU), a novel nitrosourea derivative, in a 55-year-old man with advanced-stage primary myelofibrosis. MCNU was given intravenously at a dose of 50 mg once a month. Following MCNU treatment, his anemia and splenomegaly improved markedly. An increased dose of MCNU (100 mg, once a month) was even more effective for relieving the symptoms. Severe side effects resulting from this therapy, such as leukocytopenia or thrombocytopenia, were never observed. These observations indicate that MCNU treatment may be a beneficial management of advanced-stage primary myelofibrosis.     

Abnormally Short Erythrocyte LifeSpan in Three Patients with Primary Myelofibrosis Despite Successful Control of Splenomegaly

Splenectomy is an elective operation for refractory anemia in patients with primary myelofibrosis (PMF). We found that 3/3 patients with PMF in our department continued to have very shortened erythrocyte (RBC) lifespans (35 days, 66 days, and 37 days, respectively) after treatment-alleviated splenomegaly. These outcomes suggest that intravascular hemolysis predominantly independent of hypersplenism may underlie, at least to some extent, peripheral hemolysis in patients with PMF. More cases studies are needed to elucidate the role of splenomegaly in PMF-associated anemia.     

Lenalidomide therapy in myelofibrosis with myeloid metaplasia

We present results of 2 similarly designed but separate phase 2 studies involving single-agent lenalidomide (CC-5013, Revlimid) in a total of 68 patients with symptomatic myelofibrosis with myeloid metaplasia (MMM). Protocol treatment consisted of oral lenalidomide at 10 mg/d (5 mg/d if baseline platelet count < 100 x 10(9)/L) for 3 to 4 months with a plan to continue treatment for either 3 or 24 additional months, in case of response. Overall response rates were 22% for anemia, 33% for splenomegaly, and 50% for thrombocytopenia. Response in anemia was deemed impressive in 8 patients whose hemoglobin level normalized from a baseline of either transfusion dependency or hemoglobin level lower than 100 g/L. Additional treatment effects in these patients included resolution of leukoerythroblastosis (4 patients), a decrease in medullary fibrosis and angiogenesis (2 patients), and del(5)(q13q33) cytogenetic remission accompanied by a reduction in JAK2(V617F) mutation burden (1 patient). Grade 3 or 4 adverse events included neutropenia (31%) and thrombocytopenia (19%). We conclude that lenalidomide engenders an intriguing treatment activity in a subset of patients with MMM that includes an unprecedented effect on peripheral blood and bone marrow abnormalities.     

Successful treatment with imatinib mesylate of a CML patient in megakaryoblastic crisis with severe fibrosis

The prognosis of patients with chronic myeloid leukemia in blastic crisis (CML-BC) remains extremely poor, and multiagent chemotherapy regimens commonly used to treat acute leukemia offer only short-term benefits. Therefore, the advent of the novel molecularly targeted anticancer agent imatinib mesylate is a breakthrough in CML therapy. We present a CML patient in megakaryoblastic crisis with severe myelofibrosis, who was treated with imatinib at a dosage of 400 mg/day and achieved complete remission together with a marked regression of myelofibrosis after 1 month. The effect of imatinib on the long-term prognosis remains unclear, although the agent is clearly a promising drug for treating CML-BC even in cases of myelofibrosis.     

An effective acute graft-vs.-host disease prophylaxis with minidose methotrexate, cyclosporine, and single-dose methylprednisolone.

Cyclosporine and methotrexate at standard doses (15 mg/m2 on day 1 and 10 mg/m2 on days 3, 6, and 11, total 45 mg/m2) are effective in the prophylaxis of acute graft-vs.-host disease. However, the combination has significant early toxicities with delayed engraftment, increased mucositis, and hepatotoxicity. We modified the combination by adding single-dose methylprednisolone and lowered the total dose of methotrexate to 35 mg/m2 (5 mg/m2 on days 1, 3, and 6, and then 10 mg/m2 on days 11 and 18) and then to 20 mg/m2 (5 mg/m2 on days 1, 3, 6, and 11) in an attempt to decrease these side effects in two sequential consecutive groups of patients. We demonstrated that the modified regimens maintained the efficacy with reduced toxicities. The rate of engraftment was comparable to cyclosporine alone and the hepatotoxicity was reduced with reduced doses of methotrexate. Factors such as early immunosuppression of the host, intravenous immunoglobulin, the timing of steroid administration, nucleotide free diet and germ free environment may contribute to the effectiveness of the combination and permit reduction of methotrexate dose.     

Twenty-four hour intra-arterial infusion of 5-fluorouracil, cisplatin, and leucovorin is more effective than 6-hour infusion for advanced hepatocellular carcinoma

AIM To evaluate the time dependence of intra-arterial 5-fluorouracil (5-FU) therapy for advanced hepatocellular carcinoma (aHCC).METHODS Thirty-seven adult Japanese patients who had aHCC and liver cirrhosis were treated with combined intra-arterial 5-FU, cisplatin (CDDP), and leucovorin (LV). The Japan Integrated Staging score (JIS score) of each patient was 3 or more. The patients were divided into two groups, after which the 15 patients in group S were treated with 6-h infusion chemotherapy (LV at 12 mg/h, CDDP at 10 mg/h, and 5-FU at 250 mg/m2 per 4 h) and the 22 patients in group L were treated with 24-h infusion chemotherapy (LV at 12 mg/h, CDDP at 10 mg/h, and 5-FU at 250 mg/m2 per 22 h). Continuous infusion chemotherapy was performed via the proper hepatic artery every 5 d for 4 wk using an implanted drug reservoir.RESULTS The percentages of patients with a partial response after 4 wk of chemotherapy were 6.7% in group S and 31.8% in group L. The survival of group L was significantly better than that of group S, with the median survival time being 496 d in group L and 226 d in group S (P ＜ 0.05).CONCLUSION Continuous 24-h intra-arterial infusion is more effective for aHCC and can markedly prolong survival time as compared to 6-h infusion.     

Therapeutic and neurotoxic effects of 2-chlorodeoxyadenosine in adults with acute myeloid leukemia

Despite expectations that 2-chlorodeoxyadenosine (2-CdA) would prove active primarily in lymphoproliferative diseases, early reports suggested unexpected high activity of this drug in heavily pretreated children with acute myeloblastic leukemia (AML) at a maximally tolerated dose of 8.9 mg/m2/day for 5 days. In view of these findings, we conducted an escalating dose trial of 2-CdA in adult patients with relapsed or resistant AML. Thirty-six patients who had received extensive prior therapy were treated at 9 dose levels of 2-CdA at daily doses ranging from 5 to 21 mg/m2 for 5 days. 2-CdA eliminated leukemic blasts from the peripheral blood in 32 of 36 cases; however, bone marrow hypoplasia was seen only at daily dose levels > or = 15 mg/m2. We observed a total of 3 complete remissions: 1 at the 15 mg/m2/d dose level and 2 at the 21 mg/m2/d dose level; these responses persisted for 3, 2, and 3 months, respectively. Although prolonged myelosuppression would have been dose-limiting at 21 mg/m2/d for 5 days, the most important adverse effect was the development of a sensorimotor peripheral neuropathy. This reaction, whose onset was substantially delayed after completion of drug treatment, was observed in 2 of 5 patients at the 19 mg/m2/d level and in 4 of 4 evaluable patients at the 21 mg/m2/d level. Pathologically, this process was characterized by axonal degeneration and secondary demyelination. Other side effects included reactivation of a posttransplant Epstein-Barr virus-related lymphoma in 1 patient and tumor lysis syndrome. We conclude that the maximally tolerable dose of 2-CdA in adult patients (17 mg/m2/d for 5 days) in approximately twofold in excess of that previously reported in children and that the limiting toxic effect is a degenerative neuropathic disorder. We confirm that this drug has definite activity in AML, but the magnitude of this effect needs to be determined in larger numbers of patients who have received less extensive therapy. This agent deserves further evaluation in patients with both AML and acute lymphoblastic leukemia at these higher doses and perhaps as part of a preparative regimen for patients undergoing bone marrow transplantation.     

Phase Ⅱ study of protracted irinotecan infusion and a low-dose cisplatin for metastatic gastric cancer

AIM: To test protracted irinotecan infusion plus a lowdose cisplatin in this Phase Ⅱ trial to decrease its toxicity.METHODS: The eligibility criteria were: (1) histologically proven measurable gastric cancer; (2) performance status of 0 or 1; (3) no prior chemotherapy or completion of prior therapy at least 4 wk before enrollment; (4)adequate function of major organs; (5) no other active malignancy; and (6) written informed consent. The regimen consisted of irinotecan (60 mg/m2) on d 1 and 15 by 24-h infusion and cisplatin (10 mg/m2) on d 12 2, 3,15, 16, and 17. Treatment was repeated every 4 wk.RESULTS: Thirty-one patients were registered between April 2000 and January 2001. The response rate for all 31 patients, 20 patients without prior chemotherapy, and 11 patients with prior chemotherapy was 52% (16/31),60% (12/20), and 36% (4/11), respectively. The median survival time was 378 d. The median number of courses given to all patients was 2. Grade 4 neutropenia occurred in 11 (35%) patients, while grade 3 to 4 diarrhea or nausea occurred in 1 (3%) and 3 (10%) patients,respectively. Fatigue was minimal as grade 1 fatigue was found only in 3 (10%) patients. Other adverse events were mild and no treatment-related deaths occurred.CONCLUSION: This regimen showed a high level of activity and acceptable toxicity in patients with metastatic gastric cancer.     

Phase Ⅱ study of protracted irinotecan infusion and a low-dose cisplatin for metastatic gastric cancer

AIM: To test protracted irinotecan infusion plus a low-dose cisplatin in this Phase II trial to decrease its toxicity. METHODS: The eligibility criteria were: (1) histologically proven measurable gastric cancer; (2) performance status of 0 or 1; (3) no prior chemotherapy or completion of prior therapy at least 4 wk before enrollment; (4) adequate function of major organs; (5) no other active malignancy; and (6) written informed consent. The regimen consisted of irinotecan (60 mg/m(2)) on d 1 and 15 by 24-h infusion and cisplatin (10 mg/m(2)) on d 1, 2, 3, 15, 16, and 17. Treatment was repeated every 4 wk. RESULTS: Thirty-one patients were registered between April 2000 and January 2001. The response rate for all 31 patients, 20 patients without prior chemotherapy, and 11 patients with prior chemotherapy was 52% (16/31), 60% (12/20), and 36% (4/11), respectively. The median survival time was 378 d. The median number of courses given to all patients was 2. Grade 4 neutropenia occurred in 11 (35%) patients, while grade 3 to 4 diarrhea or nausea occurred in 1 (3%) and 3 (10%) patients, respectively. Fatigue was minimal as grade 1 fatigue was found only in 3 (10%) patients. Other adverse events were mild and no treatment-related deaths occurred. CONCLUSION: This regimen showed a high level of activity and acceptable toxicity in patients with metastatic gastric cancer.     

Phase Ⅱ study of protracted irinotecan infusion and a low-dose cisplatin for metastatic gastric cancer

AIM: To test protracted irinotecan infusion plus a lowdose cisplatin in this Phase Ⅱ trial to decrease its toxicity.METHODS: The eligibility criteria were: (1) histologically proven measurable gastric cancer; (2) performance status of 0 or 1; (3) no prior chemotherapy or completion of prior therapy at least 4 wk before enrollment; (4)adequate function of major organs; (5) no other active malignancy; and (6) written informed consent. The regimen consisted of irinotecan (60 mg/m2) on d 1 and 15 by 24-h infusion and cisplatin (10 mg/m2) on d 12 2, 3,15, 16, and 17. Treatment was repeated every 4 wk.RESULTS: Thirty-one patients were registered between April 2000 and January 2001. The response rate for all 31 patients, 20 patients without prior chemotherapy, and 11 patients with prior chemotherapy was 52% (16/31),60% (12/20), and 36% (4/11), respectively. The median survival time was 378 d. The median number of courses given to all patients was 2. Grade 4 neutropenia occurred in 11 (35%) patients, while grade 3 to 4 diarrhea or nausea occurred in 1 (3%) and 3 (10%) patients,respectively. Fatigue was minimal as grade 1 fatigue was found only in 3 (10%) patients. Other adverse events were mild and no treatment-related deaths occurred.CONCLUSION: This regimen showed a high level of activity and acceptable toxicity in patients with metastatic gastric cancer.     

初发急性早幼粒细胞性白血病老年患者诊治全过程1例报告及文献复习

目的报导初发APL老年患者对ATRA联合ATO加化疗的疗效并结合文献讨论。方法采集病史,书写病程演进,作辅助检查,进行PML—RARu,融合基因检测和随访。记录治疗方案、并发症、药物不良反应及处理经过。结果本例AML—RARa融合基因阳性。采用ATRA联合ATO加化疗方案。经诱导、巩固和维持等3阶段治疗,住院5m,巩固治疗结束后,获MR。全程治疗32m完成。并发症主要是肺部感染,处理要及时,支持治疗要重视。药物治疗的计量应掌握在成人的2／3-3／4。结论老年APL患者能够耐受ATRA联合ATO加化疗并取得良好的疗效。     

Unsuccessful Treatment with Fludarabine in Four Cases of Refractory Rheumatoid Arthritis

The aim of this study was to evaluate the efficacy of fludarabine treatment in patients suffering from refractory rheumatoid arthritis. Four patients affected by refractory seropositive rheumatoid arthritis underwent treatment with fludarabine for 6 months. The drug was administered intravenously at a dose of 25 mg the first month in a single infusion, and then monthly for 5 months at a dose of 25 mg for 3 consecutive days. All four patients obtained no clinical benefit from the treatment; moreover, inflammation indices worsened and the prednisone dosage was increased during the trial, in spite of a significant fall in CD4+ T cells. In our experience low-dose fludarabine is not useful in the treatment of refractory rheumatoid arthritis. Received: 1 September 1999 / Accepted: 2 March 2000