Activity and toxicity of 2-CDA in Langerhans cell histiocytosis: a single institutional experience.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder characterized by clonal proliferation of immature and abnormal bone marrow derived langerhans cells. Treatment is usually multimodal. Potent anti-monocyte as well as immunomodulatory activity of 2-CDA and its proven efficacy in many lymphoproliferative disorders has made 2-CDA a rational choice in treatment of LCH. AIM: To evaluate the efficacy and toxicity profile of 2-CDA in children with relapsed or refractory LCH. SETTING AND DESIGN: This is a pilot study and we present the initial data of the first seven patients treated at our institution. MATERIALS AND METHODS: Seven patients of relapsed and refractory LCH were enrolled from July 2000 to June 2004. The cohort of seven patients included six males and one female with a median age at initiation of cladribine was 2.25 years (range, 1.67 to 7.0 years). Three patients had received one prior chemotherapy regimen while the rest were heavily pretreated. Cladribine was administered over two hours IV daily for five days and repeated every four weeks. RESULTS: After a median of six courses of cladribine (range, 2 to 9), two (33%) patients achieved PR and two (33%) patients have SD on imaging but are clinically better. None experienced grade 3 or 4 hematologic toxicity. At a median follow-up of 19 months (range, 8 to 52 months), five patients remain alive and one patient has died. CONCLUSION: Our study shows that single agent 2-CDA is active and well-tolerated in children with relapsed or refractory LCH.

Clinico-biologic profile of Langerhans cell histiocytosis: a single institutional study.

CONTEXT: Langerhans cell histiocytosis (LCH) is a rare atypical cellular disorder characterized by clonal proliferation of Langerhans cells leading to myriad clinical presentations and highly variable outcomes. There is a paucity of Indian studies on this subject. AIM: To present the experience of management of LCH at a single institution. SETTINGS AND DESIGN: This is a retrospective observational study of patients with LCH who presented at the Tata Memorial Hospital between January 1987 and December 2002. MATERIALS AND METHODS: Fifty-two patients with LCH were treated in the study period. Due to the long observation period and variability in diagnostic and therapeutic protocols, the patients were risk-stratified based on present criteria. The disease pattern, management approaches and treatment outcomes of patients were recorded. STATISTICAL ANALYSIS USED: Statistical analyses were done using Student's 't' test, test for proportion and survival estimates based on the Kaplan-Meier method. RESULTS: The median age at presentation was 3 years and more than 48% of the patients had Group I disease. Skeleton, skin and lymphoreticular system were the commonly involved organs. Majority (80%) required some form of therapy. The projected overall survival is 63% at 10 years and mean survival is 118 months. Seventeen percent of surviving patients developed long-term sequelae. CONCLUSIONS: The clinico-biologic profile of LCH patients in India is largely similar to international patterns except a higher incidence of lymphoreticular involvement. Majority of the patients respond favorably to therapy and have a good outcome, except a subset of Group I patients who warrant enrollment in clinical trials with innovative therapeutic strategies to improve outcome.

Brain metastasis--evidence based management.

Advances in cancer management have resulted in a significant increase in median survival of number of diseases. Consequently we are seeing more patients living long enough to develop symptomatic brain metastases. The management of such patients will be discussed here. The most important definitive investigation is contrast enhanced MRI scan of brain. Management consists of supportive care and disease directed treatment. Surgical resection remains the gold standard for the treatment of solitary brain metastases. Whole brain radiotherapy is considered standard treatment for all patients with brain metastases. The role of chemotherapy was limited in the past. Recently several new agents have been identified as potentially useful. Preliminary results indicate that drugs like temozolomide and topotecan have antitumor activity against the brain metastases as well as the primary systemic malignancies. The goal of multimodality treatment for brain metastases is to palliate local symptoms and prevent consequences of neurological involvement.

Rituximab (anti-CD20 monoclonal antibody) in lymphoproliferative malignancies: Tata Memorial experience.

Rituximab has been used extensively in lymphoproliferative disorders. We evaluated the results of 64 consecutive patients treated between 2001 and 2004 at our institution. This included 54 males and 10 females. The median age was 54 years (range 17 to 85 years). One-fourth of patients were above 60 years. The histology was aggressive NHL in 35, indolent NHL in 22 and 7 cases were diagnosed as CLL. Among NHL, sixteen were in early stage (I/II) and the remaining forty-one were in advanced stage (III/IV) of disease. B symptoms were present in 47% of cases. A total of 33 were de novo cases and 31 were previously treated. Rituximab monotherapy was used in 17 cases. Rituximab was used in combination with chemotherapy in the other 47 cases. Infusional toxicity included anaphylaxis in one, hypotension in one and minor infusional reactions in four others. The patient who developed anaphylaxis required discontinuation of further Rituximab. Growth factors were used in 25 patients. Febrile neutropenia occurred in 19 patients. The overall RR (CR + PR) was 72%. One patient had stable disease and progressive disease was documented in 17 patients. A total of seven patients died, three due to progressive disease, three due to chemotherapy related toxicity and one due to an unrelated cause. We conclude that Rituximab is a valuable addition to the treatment armamentarium of lymphoproliferative disorders.

Yolk sac tumor of vagina.

Yolk sac tumors are common in children. By virtue of being chemosensitive, they are amenable to cure by chemotherapy alone and radical surgery is often not required. Yolk sac tumors occurring in the vagina are rare and thus may not be recognized early or may be inadvertently subjected to radical surgery. The authors report a case that presented to them after radical surgery with elevated Alpha-fetoprotein level is reported. The management of this case and review of the relevant literature are discussed here.

Outcome of acute myeloid leukaemia in adults: a retrospective analysis.

BACKGROUND: There are little data from India on the management of acute myeloid leukaemia. With better understanding of the biology of the disease, and routine use of high-dose cytarabine as post-remission therapy with or without haematopoietic blood stem cell transplantation (HSCT), the results have improved in the past two decades. We analysed our results in a cohort of recently treated patients. METHODS: A total of 166 newly diagnosed patients with AML (excluding acute promyelocytic leukaemia), 15-60 years of age were treated with daunorubicin (60 mg/m2/day x3 days) or idarubicin (12 mg/m2/day x3 days) with cytarabine (100 mg/m2/day continuous i.v. infusion x7 days) induction chemotherapy. Post-remission therapy included 2 cycles of high-dose cytarabine (15-18 g/m2) followed by monthly cycles of outpatient maintenance chemotherapy x4 cycles, consisting of daunorubicin (45 mg/m2 i.v. x1 day and cytarabine 100 mg/ m2 s.c. twice daily x5 days). Six patients in remission received sibling donor allogeneic HSCT. RESULTS: Morphological complete remission was achieved in 69.9% of the patients. Resistant disease after induction chemotherapy was seen in 14.6% and early mortality occurred in 16%. Relapse-free survival and event-free survival at a median of 36 months was 34% and 22%, respectively. Relapse occurred in 43.9%. The median duration of remission was 12 months. CONCLUSIONS: Our results conform to the published literature from larger cooperative studies from the West. Currently available cytotoxic drugs are unlikely to improve the results any further.

Metastatic gastric adenocarcinoma.

Gastrointestinal tumors represent less than 5% of all pediatric neoplasms. Within this subgroup carcinomas are rare, especially that of stomach. The authors present this rare entity with an equally rare presentation.

Use of liposomal amphotericin B in bone marrow transplant.

Increasing number of transplants worldwide has resulted in an increase in the incidence of fungal infections. Prolonged neutropenia, immunosuppression and graft vs. host disease all result in high predisposition to fungal infections. The likelihood of developing a fungal infection increases with the severity and duration of neutropenia, which, in the case of cancer or chemotherapy for the treatment of hematological malignancies, can range from a few days to several weeks. Invasive fungal infections are difficult to diagnose and neutropenic patients with fever often receive empirical antifungal therapy. This provides a rationale for the prophylactic use of antifungal agents. The empirical use of liposomal amphotericin B has overcome some of the difficulties usually found in this setting. The majority of clinical efficacy data related to liposomal amphotericin B are derived from compassionate use studies and case series. The major advantage of these liposomal formulations of amphotericin B is a reduction in amphotercin toxicity. Use of liposomal amphotericin has been shown to be a cost-effective approach abroad and the same has been our experience also. Commercially ambisome and Fungisome are the only products that contain true liposomes. Unlike ambisome, which needs to be used in dose of 3 mg/kg/day Fungisome is effective in the dose of 1-3 mg/kg bodyweight. The Indian liposomal preparation has shown to be safe and effective used in over 150 transplant patients in our experience. We conclude that the liposomal amphotericin is better-tolerated and also gives,better responses in documented fungal infections.

Clinical profile of HIV infection.

OBJECTIVE: To study the clinical profile of human immunodeficiency virus (HIV) infection in children. DESIGN: Prospective. SETTING: HIV clinic at a pediatric tertiary care center in an urban metropolis. METHODS: From August 1994 onwards, 285 HIV positive children were referred to the HIV clinic. These included those intramural deliveries born to HIV positive mothers, those referred from other centers with a positive HIV ELISA (enzyme-linked immunosorbent assay) test and those screened routinely at our center in view of transfusion dependence and found to be HIV positive. After informed consent from either parent, the HIV status of all referred patients was retested by ELISA. RESULTS: Two hundred and thirteen (74.73%) patients were below the age of five years. Vertical transmission as the route of infection was documented in 247 (86.66%), 33 (11.57%) were infected through blood and in 5 (1.75%), the mode of transmission could not be ascertained. The clinical features noted were protein energy malnutrition in 127 (44.56%), pulmonary and extrapulmonary tuberculosis in 84 (29.47%), hepatosplenomegaly in 82 (28.77%), persistent generalized lymphadenopathy in 67 (23.50%), skin lesions in 63 (22.10%), chronic diarrhea in 43 (15.08%), oral thrush in 42 (14.73%), pyrexia of unknown origin in 36 (12.63%), chronic lung disease in 32 (11.22%), chronic hypertrophic parotitis in 27 (9.47%), chronic ottorrhea in 26 (9.12%), recurrent lower respiratory tract infection in 24 (8.42%), neurological manifestations of non-tuberculous origin in 13 (4.56%) and Pneumocystis carinii pneumonia in 11(3.88%). Forty-eight (16.84%) were asymptomatic, 30 (10.52%) died of AIDS during the study period and 39 (13.68%) have been lost to follow up. CONCLUSION: Vertical transmission was the commonest mode of infection. Perinatally infected children become symptomatic by five years of age. Protein energy malnutrition, hepatosplenomegaly and persistent generalized lymphadenopathy were common presenting features. Tuberculosis was the major co-infection. Chronic hypertrophic parotitis and chronic lung disease were distinguishing features of this study. Encephalopathy was associated with poor outcome.

Strategy for preventing vertical transmisssion of HIV : Bombay experience.

OBJECTIVE: To evaluate the efficacy of an interventional regime to reduce the perinatal mode of transmission of human immunodeficiency virus (HIV). DESIGN: Prospective. SETTING: Perinatal HIV clinic at a university affiliated maternity hospital. SUBJECT & METHODS: After adequate counseling, consenting HIV positive women were offered perinatal intervention: (i) administration of 400 mg of zidovudine (AZT) per day for the last 6 weeks of the antenatal period; (ii) delivery by elective Caesarian section before rupture of membrances; (iii) oral AZT powder in the dose of 8 mg per kilogram daily to the infant for the first 6 weeks of life; and (iv) avoidance of breast milk. The infants were scheduled for regular follow-up for at least 18 months. A definitive diagnosis of infectivity in the infant was ascertained by two positive enzyme-linked immunosorbent assays (ELISA) at the age of 9 months and between 15 to 18 months. RESULTS: Of the 107 mother-infant pairs enrolled, 22 infants were lost to follow-up, 15 were under 18 months of age at the time of this analysis and 2 infants died without a diagnosis. Of the remaining 68 infants followed up, 4 tested HIV positive at 18 months. Of the 229 women-infant pairs who did not receive perinatal intervention, 55 infants followed up to 15-18 months were found to be infected. CONCLUSION: This interventional strategy significantly reduced the mother to child transmission of HIV. However, the results need to be substantiated by larger studies.

Traumatic heart disease.

Five cases of traumatic heart disease (THD) who sustained blunt chest injury in road accidents are reported. In addition to fracture of the ribs (observed in all the cases), there was fracture of the sternum and rupture of the liver and spleen in one case each. Two patients had flail chest. One presented with recurrent ventricular tachycardia lasting for 72 hours followed by changes suggestive of subendocardial infarction. The second case also had changes like subendocardial infarction and it was preceded by junctional tachycardia with aberrant conduction during the first 48 hours. Ventricular premature beats (VPB) were the only abnormality noted in one case and the remaining two had ST-T wave changes suggestive of inferolateral ischaemia without any arrhythmias. The patient with VPB developed pericardial rub without effusion. There was one death and postmortem revealed ruptured liver and spleen in addition to laceration of the right ventricle and haemopericardium. The electrocardiographic changes persisted for two to eight weeks. All four cases were symptom-free at 12 weeks and treadmill exercise test done after 12 to 18 weeks was normal.