Comparison of clinical efficacy and toxicity of conventional and optimum biological response modifying doses of interferon alpha-2C in the treatment of hairy cell leukemia: a retrospective analysis of 39 patients

Hairy cell leukemia (HCL) has been shown to be extraordinarily sensitive to treatment with alpha-interferon (IFN). In order to define clinically effective IFN doses associated with minimal toxicity, the therapeutic efficacy and side effects of recombinant IFN-alpha-2C treatment of HCL were compared for two different dose regimens: 18 patients (group A) received conventional doses of recombinant IFN-alpha-2C (2 x 10(6)U/m2) for a median time of 35 weeks (range 26-52 weeks), and 21 patients (group B) received optimum biological response-modifying doses of IFN-alpha-2C (0.2-0.6 x 10(6)U/m2) for a median time of 31 weeks (range 12-52 weeks). Interferon was administered daily subcutaneously for 3 months and then every second or third day. Induction of neopterin excretion was chosen as the marker for definition of biological response. The smallest IFN dose causing maximum in vivo induction of biosynthesis of the GTP-degradation product neopterin was deemed "biologically optimal." Both dose regimens were effective, but the low-dose regimen was almost free of toxicity. Thus, in HCL patients alpha-IFN related toxicity can be separated from its antineoplastic activity. Low doses of alpha-IFN should be considered for treatment of HCL patients who develop toxic side effects and for primary treatment of HCL patients with severe cytopenia.     

Effect of active immunization to luteinizing-hormone-releasing hormone on the fertility and histoarchitecture of the reproductive organs of male rat

Summary The feasibility of using a vaccine against luteinizing-hormone-releasing factor for supression of pituitary and gonadal functions has been indicated for some time. Antibody production against this low-molecular-weight, naturally occurring decapeptide, however, requires to be coupled to a carrier protein to enhance its immunogenicity. LHRH was coupled to diphtheria toxoid (DT). Adult male Sprague-Dawley rats with a mean basal body weight of 200g were immunized with anti-LHRH-DT (20 g/injection/rat) at four-week intervals. An equal number of unexposed animals served as controls. Six animals were killed every two weeks up the end of the week 43. The vaccination schedule did not have any effect on the gain in body weight, nor was any adverse effect of vaccination observed in the course of the investigations. The pituitary, prostate, epididymis, testes, seminal vesicles, adrenal and thyroid were excised for determination of organ weight and histological examination. The adrenal, pituitary and thyroid showed no remarkable weight changes during the observation period, whereas the weights of the reproductive organs demonstrated significant reductions compared to those of the control group. The histopathology revealed marked to significant changes in the gonads and the accessory sex organs including the prostate. A progressive phase of regeneration of spermatogenesis was evident 98 days after vaccination. Total recovery of spermatogenesis was observed 300 days after vaccination. The mating studies showed the return of fertility 300 days after vaccination. The litters borne were normal. Prostate showed recovery after 154 days of vaccination. Our observations lend strong support to the hypothesis that anti-LHRH vaccine can be effectively used on the management of prostate carcinoma. If the vaccination is given together with a suitable dose of long-acting androgen, contained in an adequate delivery system, the regimen may be used for the regulation of male fertility.     

Fludarabine in combination with alemtuzumab is effective and feasible in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: results of a phase II trial.

PURPOSE: To determine the efficacy and safety of a newly developed concomitant administration of fludarabine and alemtuzumab (FluCam) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). PATIENTS AND METHODS: A total of 36 patients were treated in this phase II study (median age, 61.47 years; mean number of prior chemotherapies, 2.6; Binet stage C, n = 28). After an initial dose escalation of alemtuzumab over 3 days, alemtuzumab 30 mg and fludarabine 30 mg/m2 were administered on 3 consecutive days. Treatment was repeated after 28 days for up to six cycles. Restaging (following National Cancer Institute criteria) was carried out after cycles 2 and 4 and 1 month after the end of treatment. RESULTS: The overall response rate was 83% (11 complete responses, 19 partial responses, one stable disease, and five progressive diseases). Two patients with progressive disease developed fungal pneumonias, and one patient died as a result of Escherichia coli sepsis. Two subclinical cytomegalovirus reactivations occurred. CONCLUSION: The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL.     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Purging of acute myeloid leukemic cells by ether lipids and hyperthermia

Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro.     

完全腹腔镜Roux—en—Y吻合术式应用于远端胃癌根治术20例

目的探讨完全腹腔镜Roux．en—Y吻合术式应用于远端胃癌根治术的安全性和可行性。方法回顾性分析福建省肿瘤医院腹部外科2012年8月至2013年3月对腹腔镜胃大部切除术后实施完全腹腔镜Roux．en—Y吻合术的20例胃癌患者的术中和术后临床资料。结果20例患者均成功实施完全腹腔镜远端胃癌根治术,无一例中转开腹或中转腹腔镜辅助手术。手术时间（190．8±53．6）min,术中出血量（122．4±57．7）ml,淋巴结清扫数（31．2±5．7）枚,术后病理切缘均为阴性。术后排气时间为（2．6±1．6）d,住院时间为（8．1±2．0）d。有1例术后出现肺部感染,但无吻合术相关并发症发生。结论完全腹腔镜Roux—en—Y吻合术式应用于远端胃癌根治术安全且可行。