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.

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.

Oral cancers in Mumbai, India: a fifteen years perspective with respect to incidence trend and cumulative risk.

OBJECTIVE: We estimated the time trends in the incidence and the risk of developing an oral cancer in Mumbai, Indian population using the data collected by the Bombay Population Based Cancer Registry during the 15 year period from 1986 to 2000. METHODS: A total of 9,670 oral cancers (8.2% of all neoplasms) were registered, of which 6577 were in males and 3093 in females (10.7% and 5.4% of the respective totals for the two genders). For evaluation of the trend, we applied a linear regression model based on the logarithm of the observed incidence rates. The annual percentage changes were also computed for the incidence rates to evaluate the time trend. RESULTS: In males, a statistically significant decreasing trend in the overall age-adjusted incidence rates were observed during the period 1986 to 2000, with an yearly decrease of 1.70%. This decrease was significant for men above the age of 40, but for young adult men below the age of 40, there was no significant decrease, the level being stable. In females, the overall decreasing trend in the age-adjusted incidence rates of oral cancers was not significant, but in the age group 40-59, a significant decline was observed. The probability estimates indicated that one out of every 57 men and one out of every 95 women will contract any oral cancer at some time in their whole life and 97% of the chance is after he or she completes the age of 40. CONCLUSION: The observed decreasing trend in oral cancers in Indian men may be attributed to a decrease in the usage of pan and tobacco. The high prevalence of the usage of smokeless tobacco among young adult men and women may explain the stable trend in oral cancer incidence in this group. These findings help to strengthen the association between tobacco use and oral cancer risk.

Imatinib in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of gastrointestinal tract. The tumors express the cell surface transmembrane receptor KIT that has a tyrosine kinase activity and is a protein product of KIT protoeoncogene. These tumors occur in the whole of Gastrointestinal tract. Treatment includes surgical resection for localized tumors. For metastatic disease treatment options include systemic chemotherapy, radiation therapy, with a response rate of less than 10%. Presently Imatinib; a tyrosine kinase inhibitor has shown promising result with response rates upto 59-69% in phase II results in metastatic setting; and ongoing phase II & phase III trials in adjuvant setting will help to establish its role as an adjuvant to surgery. We have treated eleven patients of metastatic GIST with Imatinib and we hereby present these cases.

Antilymphocyte globulin (ALG) or antithymocyte globulin (ATG) with methylprednisone and oxymethalone in aplastic anaemia.

From 1986 to 1994 we treated 26 patients of aplastic anaemia between 6 to 61 years age group with ATG/ALG, Methylprednisone and Oxymethalone. Five had very severe aplastic anaemia, 16 had severe and 5 nonsevere disease. Disease was associated with hepatitis in 5 patients and with pregnancy and drug use in 2 patients each. In others no cause could be ascertained. A total of 31 courses of treatment were given (range 1-3 courses per patient). Nine patients had complete response (34.62%) and 3 had partial response (11.54%) with an overall response rate of 46.16%. Four patients died within 2 months of starting the treatment. The median follow up was 24 months (range 6-102 months) with an overall survival probality of 45% at 2 yr. At the time of evaluation 12 patients have died, 9 are alive disease-free and 5 are alive with disease. The side effects associated with therapy were tolerable and did not require cessation of therapy in any patient. We conclude that ATG/ALG with Methylprednisone and Oxymethalone is beneficial to significant number of patients with aplastic anaemia.

A soluble preparation from developing groundnut seeds (Arachis hypogaea) catalyzes de novo synthesis of long chain fatty acids.

A 100,000 x g supernatant fraction prepared from developing groundnut seeds (30-35 days after flowering) catalyzed the synthesis of fatty acids from [l-14C]acetate at a rate of 120nmoles of acetate incorporated per hr per gram fresh weight of tissue. 90% of this incorporated label was associated with fatty acids. The major fatty acids formed were stearic- (77%) and palmitic acids (14%) with 4% of oleic acid. The fatty acid synthetase activity was stable when stored at 0-4 degrees C for at least fifteen days. It is concluded from these results that acetyl-coA carboxylase and all the enzymes of fatty acid synthetase from developing groundnut seeds are soluble.

Purification and partial characterization of acyl carrier proteins from developing oil seeds of pisa (Actinodaphne hookeri) and ground nut (Arachis hypogaea).

Acyl carrier proteins (ACP) were purified to homogeneity in the active form from developing seeds of pisa (Actinodaphne hookeri) which synthesizes exclusively trilaurin and from ground nut (Arachis hypogaea) which synthesizes triacylglycerols containing long chain fatty acids. Two major isoforms of ACPs were purified from developing pisa seeds using DEAE-cellulose, Superose-6 FPLC and C4 reversed phase HPLC chromatographic methods. In contrast, only a single form of ACP was present in ground nut seeds which was purified by anion-exchange and activated thiol-Sepharose 4B affinity chromatography. The two isoforms of ACPs from pisa showed nearly the same specific activity of 6,706 and 7,175 pmol per min per mg protein while ground nut ACP showed a specific activity of 3,893 pmol per min per mg protein when assayed using E. coli acyl-ACP synthetase and [1-14C]palmitic acid. When compared with E. coli ACP, the purified ACPs from both the seeds showed considerable difference in their mobility in native PAGE, but showed similar mobility in SDS-PAGE under reducing conditions. In the absence of reducing agents formation of dimers was quite prominent. The ACPs from both the seed sources were acid- and heat-stable. The major isoform of pisa seed ACP and the ground nut ACP contain 91 amino acids with M(r) 11,616 and 1,228 respectively. However, there is significant variation in their amino acid composition. A comparison of the amino acid sequence in the N-terminal region of pisa and ground nut seed ACPs showed considerable homology between themselves and with other plant ACPs but not with E. coli ACP.