Adult Acute Lymphoblastic Leukemia: Results of an Aggressive Regimen in India

A total of 42 adults with acute lymphoblastic leukemia were treated with an aggressive induction/consolidation chemotherapy (MCP-841) between June 1986 and December 1991. 32 patients (76.19%) achieved complete remission at the end of induction. There were 9 induction deaths, 6 of them due to infection. All patients received cranial irradiation in the dose of 20 Gy and intrathecal methotrexate for CNS prophylaxis. Twelve patients relapsed, 10 in the bone marrow, one case had isolated CNS relapse and the other relapsed in the bone marrow and CNS. The actuarial overall survival of all patients at the end of 5 years was 41.94%. Patient characteristics including age, sex, FAB morphology, phenotype, WBC count, platelet count and LDH did not influence survival significantly.     

High dose chemotherapy for the treatment of malignant brain tumors

Conventional treatment of malignant high grade gliomas includes maximal resection followed by external beam radiotherapy. The addition of adjuvant chemotherapy has provided little improvement in the median duration of survival for these patients, particularly those patients with glioblastoma multiforme. The failure of conventional dose chemotherapy to improve the outcome of patients with high grade brain tumors has led several investigators to utilize high dose chemotherapy in order to overcome the limited benefit seen with conventional dose therapy which is due to intrinsic drug resistance as well as the impermeability of blood brain barrier. The majority of published studies utilizing this approach suggest that the addition of high dose chemotherapy with bone marrow transplant is of marginal benefit. However, most of these trials include small numbers of patients with advanced, refractory disease. A few trials have been reported utilizing high dose therapy in an adjuvant setting and the data from these studies are somewhat more promising. This review will analyze these studies and also discuss possible modifications of this approach in order to improve this aggressive treatment for patients who otherwise would have a dismal prognosis.     

Systemic treatment of skin candidosis: a randomized comparison of terbinafine and ketoconazole

Terbinafine is an antimycotic drug which has a much higher in vitro activity against dermatophytes than against yeasts. To investigate the clinical relevance of these in vitro data, 118 patients with cutaneous candidosis were enrolled in a randomized, double-blind study and allocated to a 4-week treatment with a daily dose of either 250 mg b.i.d. terbinafine or 200 mg once-daily ketoconazole. At the final assessment, 3 weeks after cessation of therapy, mycological cure rates (negative culture and negative microscopy) were 82% in the terbinafine group and 73% in the ketoconazole group. Effective treatment with negative mycology and no or minimal signs or symptoms could be achieved in 65% of those who received terbinafine and in 57% of those randomized to ketoconazole. Five per cent and 7% of the patients taking terbinafine and ketoconazole, respectively, complained about adverse events, which were usually mild and did not lead to discontinuation of treatment. In one patient in the ketoconazole group, abnormal liver enzymes were noted at the final laboratory assessment. The results of this study indicate that terbinafine 500 mg daily can be an alternative to ketoconazole when systemic treatment of skin candidosis is required.     

以顺氯氨铂为主的联合化疗方案治疗晚期肿瘤的疗效观察

本文报道我院自１９８９年９月～１９９２年１２月应用以顺氯氨铂为主的联合化疗方案治疗晚期恶性肿瘤３１例的结果。本组患者病期均较晚，故采用ＤＤＰ２Ｏｍｇ或４０ｍｇ，连用５天或３天，每次低剂量方案。３１例中，部分缓解１１例，有效率３５．５％（１１／３１）。稳定１６例，进展４例。毒性反应轻，有轻度恶心呕吐，对造血机能影响小，对肝肾等没有重大损害。结果表明低剂量ＤＤＰ为主联合化疗方案是有效而毒副反应小的方案。     

Pulmonary tuberculosis in ahmedabad: Epidemiology,diagnosis and short course chemotherapy

Five hundred children below the age of 12 years suffering from lung tuberculosis viz., primary complex (PC) or progressive primary complex (PPC) were studied. Diagnosis was based on Kenneth Jones criteria; selected cases having score of 5 or more. One hundred and eighty cases of PC were given A-1 (6 RH) regimen, while 312 cases of PPC were given A-2 (2SHRZ/4 RH) or A-3 (2 SRH/4 RH) or A-4 (2 RHE/4 RH) regimen. Follow-up was done for 6 months after completing the treatment to observe the relapse rate. In cases of PC, 6 RH regimen appeared adequate and cheaper with no relapse rate. In cases of PPC with short course chemotherapy, compliance of patients had been very good. Relapse rate was upto 13% which is acceptable. Drug toxicity was very low.     

Hematologic toxicity during craniospinal irradiation: The impact of prior chemotherapy

The purpose of this work was to determine the frequency of hematologic toxicity during craniospinal radiation (CSI) and the impact of preirradiation chemotherapy on this frequency. The charts of 37 patients who received CSI were reviewed. Twenty did not have prior chemotherapy (CT—), while 17 did receive 1 to 18 (mean 5) cycles of multi-agent systemic chemotherapy (CT+). Leukopenia/thrombocytopenia necessitating treatment interruptions occurred in 1/20 (5%) in the CT— group, compared to 8/17 (47%) among the CT+ group. This difference was statistically significant, P < 0.0001 (Fisher's exact two-tailed test). The duration of treatment interruption in the CT+ patients was 4–24 days (mean 14). Compared to the CT— group, the CT+ group had a statistically significant greater decline in their white blood cell count (WBC), platelet count, and hematocrit (HCT) during CSI (percent reduction per Gy; (P = 0.018, 0.006, and 0.047, respectively). Although not statistically significant, the CT+ group also experienced lower nadir ratios (nadir count/baseline count) in terms of WBC and platelets (P = 0.07 and 0.22, respectively). While the mean pretreatment baseline blood counts were lower in the CT+ group compared to the CT— group, these differences reached statistical significance for the HCT (P = 0.02), but not the WBC (P = 0.59) or platelets (P = 0.43). Leukopenia and thrombocytopenia are very common in patients who receive craniospinal irradiation following multi-agent systemic chemotherapy. This appears to be due to more rapid and marked reductions in counts during CSI. Since this toxicity may cause treatment interruptions that are potentially therapeutically disadvantageous, aggressive hematologic support with transfusions and growth factors may be necessary. This problem may become more common as combined modality therapy is used more frequently. © 1995 Wiley-Liss, Inc.     

Growth, puberty and obesity after treatment for leukaemia

Final height, body proportions, pubertal growth and body mass index were studied retrospectively in 142 survivors of acute lymphoblastic leukaemia (ALL). Treatment consisted of combination chemotherapy and cranial irradiation (18 or 24 Gy). Significant standing height loss and disproportion, with a relatively short back, was seen in both radiation dose groups. Girls were more severely affected than boys. Pubertal growth was adversely affected, with a reduction in peak height velocity in both sexes. Puberty occurred early in girls but at the normal time in boys. Nearly half the group were obese at final height, with no significant difference in incidence between the sexes. The relative roles of cranial irradiation and chemotherapy in the disturbance of growth, puberty and body composition observed in survivors of childhood ALL remain unclear. The aetiology is almost certainly multifactorial, with radiation-induced growth hormone insufficiency, early puberty, steroids and chemotherapy all having a role.     

Osteosarcoma of the trunk treated by multimodal therapy: Experience of the cooperative osteosarcoma study group (COSS)

The case histories of all patients with osteosarcoma of the trunk entered into the consecutive studies COSS 80 through COSS 86 of the Cooperative German/Austrian Osteosarcoma Study Group (COSS) were analyzed in order to evaluate their clinical characteristics and the impact of modern neoadjuvant therapy on prognosis. They were compared to those of all patients with extremity osteosarcoma treated according to the same protocols. While tumors of the trunk comprised only 32 (4.8%) of 665 primary classical osteosarcomas, secondary osteosarcomas were much more likely to be located in bones of the axial skeleton (6 of 18, 33%). Patients with primary osteosarcoma of the axial skeleton were older (mean: 20.8 vs. 15.2 years, P < 0.01) and were more likely to present with metastases at diagnosis (34% vs 12%, P < 0.001) than those with primary extremity osteosarcoma. In contrast to extremity tumors, local surgical treatment failure was very common in osteosarcomas of the trunk. Complete tumor removal was achieved in less than half of all evaluable cases. The prognosis of eight patients with localized primary axial osteosarcoma and effective surgical local control was not inferior to that of 483 equally evaluable patients with extremity tumors. In conclusion, while secondary systemic spread of axial osteosarcoma may be avoided in patients treated with multiagent chemotherapy, successful treatment is often barred by primary metastatic disease and inability to control the local tumor site. © 1995 Wiley-Liss, Inc.     

G-CSF in the Biology and Treatment of Acute Myeloid Leukemias

Granulocyte colony-stimulating factor (G-CSF) is an hemopoietic growth factor produced by fibroblasts, monocytes and endothelial cells. The role of G-CSF in the biology of acute myeloid leukemia (AML) has been investigated by several authors, who have demonstrated receptor mediated enhanced proliferation of AML blasts in vitro, in the presence of G-CSF. This effect is further increased by addition of other cytokines such as GM-CSF, IL3, IL4, Stem cell factor (SCF), while Tumor Necrosis Factor (TNF) and Transforming Growth Factor β1 (TGF β1) seem to exert an inhibitory activity. An autocrine production of G-CSF by AML cells, a paracrine production by accessory cells and a protective effect displayed by G-CSF against programmed cell death could partially contribute to explain the pathogenesis of AML. In vivo, G-CSF has been used after chemotherapy in AML, in order to improve hemopoietic recovery in patients at high risk of infection. Current studies are focusing on better definition of the role of G-CSF, as such or combined with other biological modifiers, in dose intensification and autologous bone marrow or peripheral blood stem cell transplantation.     

Phase II study of amonafide in patients with recurrent glioma

Summary Amonafide, a novel imide derivative with broad preclinical antitumor activity, achieves significant cerebrospinal fluid levels in animal models. In order to test its antitumor activity in patients with recurrent diffuse infiltrative glioma of the astrocytic and oligodendroglial type, we performed a phase II clinical trial. Of the 22 eligible and evaluable patients treated, 2 (9%) experienced tumor regression lasting more than one year. No other patients experienced tumor regression; one remained stable more than six months. Toxicities consisted primarily of myelosuppression, vomiting, and venous irritation at the infusion site. We conclude that amonafide has minimal activity in recurrent glioma patients. Further investigations are not warranted in this study population.