Antibodies against 9-O-acetylated sialic acids in childhood acute lymphoblastic leukemia: a two-year study with 186 samples following protocol MCP 943.

Initial studies have revealed an enhanced surface expression of 9-O-acetylated sialoglycoconjugates (9-OAcSGs) on lymphoblasts concomitant with high titers of antibodies (anti-9-OAcSGs) in childhood acute lymphoblastic leukemia (ALL). This study was undertaken in 186 coded samples from 69 ALL patients to evaluate if antibodies against these sialoglycans could monitor response to the treatment. An ELISA was developed using bovine submaxillary mucin (BSM) containing high % of 9-O-acetylated sialic acids (9-OAcSA) as the capture antigen, to investigate serum levels of anti 9-OAcSGs in a single-center series of pediatric, clinically-diagnosed and immunophenotypically confirmed ALL patients, as compared to 130 healthy controls. At presentation, a 3.8-fold increase in anti-9-OAcSGs levels was detected in 63/69 ALL patients (mean +/- SEM was 102.8 +/- 6.3 microg/ml) as compared to normal controls (27.17 +/- 0.76 microg/ml), assay sensitivity being 91.3%. On an individual basis (n = 25) in patients who were longitudinally monitored for two years, a significant decline in their mean +/- SEM of OD405 was observed from 0.85 +/- 0.06 to 0.28 +/- 0.03. Additionally, a dot-blot was developed to evaluate the proportion of immune-complexed 9-OAcSGs in these patients employing achatinin-H, a 9-OAcSA-binding lectin. Our data indicate that these economically viable ELISA-based approaches allow for reliable, sensitive and rapid diagnosis of ALL. We contend that these disease-specific antibodies could be considered as potential markers both for the initial diagnosis of ALL and possibly for longitudinal monitoring of the disease.

Desmoplastic small round cell tumor: extra abdominal and abdominal presentations and the results of treatment.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare malignant neoplasm of adolescent males. Current multimodality treatment prolongs life and rarely achieves cure. AIM: To review the presenting features, histopathology and outcome of 18 patients with DSRCT treated at a single institution. SETTING AND DESIGN: This is a retrospective observational study of patients with DSRCT who presented at the Tata Memorial Hospital between January 1994 to January 2005. MATERIALS AND METHODS: Eighteen patients of DSRCT seen during this period were evaluated for their clinical presentation, response to chemotherapy and other multimodality treatment and overall survival. The cohort of 18 patients included 11 males (61%) and 7 females (39%) with a mean age of 16 years (Range 1(1/2)--30 years). Majority (83%) presented with abdomino-pelvic disease. The others, involving chest wall and extremities. There were 6 patients (33%) with metastatic disease at presentation. RESULTS: The treatment primarily included a multimodality approach using a combination of multiagent chemotherapy with adjuvant surgery and radiotherapy as applicable. A response rate of 39% (CR-1, PR-6), with chemotherapy was observed. The overall response rate after multimodality treatment was 39% (CR-5, PR-2). The overall survival was poor except in patients who had complete excision of the tumor. CONCLUSION: 0 Abdomino-pelvic site was the commonest presentation, the disease can occur at other non-serosal surfaces also. Despite aggressive treatment the outcome was poor. However, complete surgical excision seems to provide a better survival.

Isolated testicular relapse in acute lymphoblastic leukemia - effective treatment with the modified CCG-112 protocol.

BACKGROUND: The testes have been considered a sanctuary site for leukemic cells and testicular relapses used to account for a major proportion of the poor outcome of boys with acute lymphoblastic leukemia. With use of aggressive chemotherapy which includes intermediate or high dose methotrexate, the incidence of testicular relapses has declined. However once these patients have received cranial irradiation as a part of the front line protocol, high dose methotrexate needs to be avoided because of risk of developing leucoencephalopathy. AIM: To study the use of non cross resistant chemotherapeutic agents along with a regimen containing lower doses of methotrexate in patients of isolated testicular relapse (ITR). MATERIALS AND METHODS: This is a retrospective analysis of 12 consecutive patients with ITR treated with modified version of the CCG-112 protocol which consists of intensive systemic chemotherapy, cranial chemoprophylaxis along with testicular irradiation. RESULTS: One patient died of regimen related toxicity. Two patients relapsed in the bone marrow during maintenance. Of the nine patients who completed treatment, eight are alive and in remission. One patient had a bone marrow relapse two months after completing treatment. The Kaplan Meier estimates give us an Event Free Survival (EFS) of 66.7% at 10 yrs. CONCLUSIONS: Thus, though the incidence is very low, patients with ITR should be treated aggressively since they have an excellent chance of achieving a long term EFS.

Immune-mediated thrombocytopenia following dactinomycin therapy in a child with alveolar rhabdomyosarcoma: the unresolved issues.

The authors report a case of severe dactinomycin-induced thrombocytopenia in a child with alveolar rhabdomyosarcoma. The phenomenon is consistent with an immune process leading to the formation of platelet-specific antibodies. This study shows that this can be induced even with the first dose of actinomycin, and its persistence is unpredictably prolonged and does not correlate linearly in an inverted fashion with the platelet count. It will be important to identify the subsets of patients who can develop this phenomenon by molecular techniques and to define the exact mechanism in vitro leading to formation of these antibodies. This would facilitate profiling the therapy, preventing the need for multiple platelet transfusions with their obvious hazards.