Nair Cn

Therapy-Related Leukemia

5 patients developed acute nonlymphocytic leukemia (ANLL) 2–4 years following the use of various cytotoxic agents for other primary disease. Alkylating agents were responsible for development of ANLL in 3 patients while mitomycin-C and methotrexate appear to be linked with leukemia transformation in the remaining 2 patients. 3 patients had a prolonged preleukemic phase preceding ANLL. Pancytopenia observed in 4 of 5 patients favors drug-induced stem cell damage leading to relatively resistant leukemia. Although the incidence of secondary leukemia is not very high, careful use of cytotoxic agents is needed to minimize therapy-linked neoplasms.

Nasopharyngeal carcinoma in children: ten years' experience at the Tata Memorial Hospital, Mumbai

PURPOSE To evaluate the disease characteristics and outcome of children with nasopharyngeal carcinoma treated at the Tata Memorial Hospital, Mumbai. METHODS AND MATERIALS Between 1990 and 2000, 81 pediatric patients with a diagnosis of nasopharyngeal carcinoma were treated at the Tata Memorial Hospital. The median age was 14 years. The male/female ratio was 2.8:1. Of the 81 patients, 32 (39%), 21 (26%), and 28 (35%) had T1-T2, T3, and T4 (TNM International Union Against Cancer staging system, 1997), respectively. Ninety-one percent presented with nodal metastasis. Thirty patients (37%) had lymph nodes >6 cm, and 45 (56%) had bilateral nodes at presentation. Histologically, 77 patients (95%) had undifferentiated carcinoma. Eighty-five percent received neoadjuvant multiagent chemotherapy containing bleomycin, methotrexate, and cisplatin, followed by radiotherapy (RT). RESULTS After a median follow-up of 50 months, the disease-free survival (DFS) and overall survival (OS) rate for the entire group was 45% and 54%, respectively. Kaplan-Meier curves were used for evaluation of prognostic factors and were compared using the log-rank test. Nodal status had a significant impact on DFS (p = 0.021) and OS (p = 0.006). Complete responders to chemotherapy had superior DFS (p = 0.000) and OS (p = 0.000). RT doses >60 Gy resulted in better DFS (p = 0.020) and OS (p = 0.012). Combined chemotherapy plus RT resulted in improved DFS (p = 0.457) and OS (p = 0.296), although the difference was not statistically significant. CONCLUSION Combined modality management using chemotherapy and RT resulted in satisfactory locoregional control and OS in pediatric patients with nasopharyngeal carcinoma. Nodal involvement, response to chemotherapy, and RT dose were important prognostic factors.

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.

Anterior chemotherapy in esophageal cancer

Front loading chemotherapy using methotrexate (200 mg/m2) alone or methotrexate (200 mg/m2) with cisplatin (20 mg/m2 daily for 5 days) was used in epidermoid carcinoma of esophagus. Evaluation after two courses showed objective response of 50% or greater in 48% of patients with metbotrexate alone. Response rate was increased to 76.2% with addition of cisplatin to methotrexate. Small lesions (less than 10 cm) showed better response as compared to advanced cases. Therapy was generally well tolerated and good palliation was obtained even after the first course. Postchemotherapy treatment either with surgery or radiotherapy was tolerated without any major complications. The data confirm the short‐term usefulness of initial chemotherapy with methotrexate and cisplatin in esophageal cancer. Results of prolonged follow‐up will help to evaluate the role of front loading chemotherapy on long‐term survival. Cancer 56: 1502‐1506, 1985.

Karyotypic findings as an independent prognostic marker in chronic myeloid leukaemia blast crisis

Fifty-three patients with Ph positive chronic myeloid leukaemia in blastic phase were studied. Additional abnormalities were found in 29 (55%) patients and were more common in myeloid (64%) than lymphoid (45%) blast crisis. The most frequent were +Ph (32%), +8 (28%), +19 (19%), +20 (9%) and +21 (9%). i(17q) (9%) was associated with thrombocytopenia (5/5) and basophilia (2/5). The incidence of additional abnormalities was higher in patients treated with busulphan (70%) than hydroxyurea (44%). No significant differences were noted in the mean values of the clinical and haematological findings recorded at blast crisis between patients with only Ph positive (PP) cells and those with additional abnormalities (AP + AA). Univariate analysis identified karyotypic findings as an independent prognostic marker indicating its significance in assessing the response to therapy and survival after the onset of transformation.

Outpatient Antimicrobial Protocol for Febrile Neutropenia: A Nonrandomized Prospective Trial Using Ceftriaxone, Amikacin, and Oral Adjuvant Agents

Broad-spectrum antimicrobial therapy has revolutionized the management of febrile neutropenia (FN) in cancer patients. In vogue is an effective therapy an an outpatient basis. One thousand three hundred episodes of FN observed in 70 pediatric solid tumors (STs) and 65 cases of hematomalignancy (HM) at a median age of 5.5 years were treated with a protocol using once-a-day injectable ceftriaxone plus amikacin and other oral adjuvant antimicrobial agents. The mean duration of FN in the ST group was 4.0 +/- 1.2 days and in the HM group was 5.0 +/- 2.5 days. The mean duration of antimicrobial cover in the ST group was 5.0 +/- 1.75 days and in the HM group was 6.0 +/- 1.5 days. The overall recrudescence rate was 6% and the mean duration to recrudescence was 4 +/- 1.5 days (range 3-6 days). The objectives of this protocol were cost reduction and utilization of the available inpatient resources optimally by reducing the pressures of hospitalization for febrile neutropenia. We concluded that a selected group of patients with FN can be effectively managed with this regimen on an outpatient basis.

All-Trans-Retinoic Acid (ATRA): Pediatric Acute Promyelocytic Leukemia

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloblastic leukemia (AML). In this report, we present the clinical features, management, and outcome of pediatric patients with APL treated with all-trans-retinoic acid (ATRA). Of 52 newly diagnosed cases of APL between February 1992 and December 1996, 15 were in the pediatric age group (younger than 15 years). Four patients were treated with ATRA alone and 11 were allocated to receive ATRA followed by chemotherapy. Eighty-six percent of the patients achieved a complete response. The patients who received ATRA alone as maintenance therapy had relapses with a median duration of remission of 8 months (range 6-12). The patients who received ATRA, followed by consolidation chemotherapy, had a prolonged duration of remission, with a median of 20 months (range 13-28). In addition, rapid correction of coagulopathy was observed in these patients. The median duration for correction of coagulopathy was 7 days (range 5-11) and the median duration for recovery from neutropenia after chemotherapy was 10 days (range 7-20). Two major side effects of ATRA were hyperleukocytosis and retinoic acid syndrome. Significantly prolonged disease-free survival was seen in patients who received ATRA with chemotherapy. APL is not uncommon in the pediatric age group. ATRA was well-tolerated by these patients. Consolidation with chemotherapy helps in prolonging the disease-free survival in patients with APL in comparison to treatment with ATRA alone.

Pattern of subtypes of acute lymphoblastic leukemia in India

Leukemic cells from 124 acute lymphoblastic leukemia (ALL) and 31 chronic lymphatic leukemia (CLL) were examined for sheep erythrocyte receptor (E), surface immunoglobulin (SIg) and their reactivity with a panel of monoclonal antibodies recognizing specific surface antigens including pan-T, Common ALL and Ia antigens. In acute lymphatic leukemia, 33% of patients reveal T-cell receptor associated with higher age group, mediastinal mass and high WBC count. Common ALL was predominant between 2 and 9-yr age group. Among chronic lymphatic leukemia, 2 patients were found to be T-CLL while 29 revealed presence of SIg. Ia antigen was detected in 44.4% of ALL and 64% fo CLL patients. The pattern of surface marker observed in our series may be related to our life style, socio-economic and environmental factors.

Retinoblastoma: problems and perspectives from India.

This study examined the salient clinical and epidemiological characteristics of retinoblastoma (RB) in India, thereby highlighting the problems encountered there. The epidemiological characteristics of 296 patients with RB over 8 years were evaluated using hospital records and postal follow-ups. Unilateral disease was seen in 61.8% of patients. The overall median age at presentation was 3.5 years (3.5 years for unilateral RB and 1.0 years for bilateral RB). The male/female ratio was 1.4:1. The median duration of symptomatic disease was 8 months. Consanguineous marriage was seen in 17% and family history of RB was noted in 1.7% cases. Also, 2% had a history of other malignancy in the family. Associated congenital malformation was seen in 10.5% of cases. A second malignancy was seen in 0.67% of cases at a mean duration of 4.5 years after completion of therapy. A predominance of advanced-stage disease (74.5% had Reese-Ellsworth group IV and V disease) was seen in our series. Only 43.6% of patients had disease localized to the globe without any infiltration/invasion. The majority of cases had advanced-stage disease at presentation and came from the underprivileged class of society. Patients with bilateral RB presented much earlier than those with unilateral disease. In patients with unilateral RB, higher age at presentation as well as advanced disease may be related to much delay in seeking medical attention. In view of the advanced stage at presentation, there also exist a possibility of difference in the biology of the tumor seen in these patients.

Chromosomal characteristics of chronic and blastic phase of chronic myeloid leukemia. A study of 100 patients in India.

We report the cytogenetic findings of 100 patients with chronic myeloid leukemia (CML) [72 patients in chronic phase (CP) and 28 patients in blastic phase (BP)]. Of the 95 Ph + patients, six had Ph variant translocations involving chromosomes 1, 6, 7, 10, and 12. The percentage frequency of patients with chromosomal changes other than Ph was 7.3%. The additional aberrations (e.g., + Ph, + 8, i(17q), and + 19 were observed in 66.6% of BP patients. Of these anomalies, the frequency of + Ph and + 19 was higher in our patients than the incidence reported in literature. The association of + Ph and + 19 in patients with extramedullary T-cell blast crisis is an unusual finding as compared with reports in the literature and could be explained by geographic heterogeneity. The extra chromosomal abnormalities were almost absent in lymphoid blast crisis patients with blast phenotype of common acute lymphoblastic leukemia (ALL) type. Discrepancies were noted in different tissues (bone marrow and lymph node) in patients with extramedullary blast crisis of both myeloid and lymphoid type. These findings indicate the cytogenetic correlation with clinical and morphological picture, which consequently implicates the diagnostic and prognostic significance of chromosomal aspects.