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Biomedical subjects

P A Kurkure

Publications and source records attributed to P A Kurkure.

At least 19 recordsLinked to original sources

Primitive neuroectodermal tumor (PNET) as second malignancy after treatment of Hodgkin's disease.

Hodgkin's disease survivors are at an increased risk of developing second malignant neoplasms including secondary bone tumors. Common secondary bone tumors are osteogenic sarcoma and fibrosarcoma. Secondary primitive neuroectodermal tumor is extremely rare in this group. We present below, a rare case of secondary PNET in an 8-year-old child with Hodgkin's disease which developed unusually early outside the radiation portal and discuss potential factors responsible for its causation.

Antineoplastic Combined Chemotherapy Protocols↗

Constitutional and somatic RB1 mutation spectrum in nonfamilial unilateral and bilateral retinoblastoma in India.

An epidemiologic survey has indicated a comparatively high prevalence of retinoblastoma (Rb) in Asian countries. Recently, the development of preventive strategies in nonfamilial Rb has become a major goal. The present studies were designed for identification and characterization of constitutional and somatic RB1 gene mutations by conventional cytogenetics, fluorescent in situ hybridization (FISH) and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP)-DNA sequencing. Of 34 patients 32 were nonfamilial and 2 were familial Rb. Maternal inheritance of del (13q14) was common. FISH was sensitive in detecting monoallelic RB1 deletion/deletion mosaicism as a first genetic hit in 20% of cases. Somatic and germline RB1 point mutations affected exons 3, 17, 20, and 21 and these were identified as novel mutations. Involvement of exon 20 as a predisposing mutation in sporadic unilateral retinoblastoma (URB) probably suggests the susceptibility of exon 20 to unknown etiologic factors in our population. A de novo RB1 deletion along with transmitted RB1 point mutation from an asymptomatic parent was identified as a unique predisposing RB1 mutation chimerism in a URB case that later evolved to bilateral retinoblastoma (BRB). The predisposing mutations such as del (13q), RB1 mono-allelic deletion and RB1 point mutation in sporadic Rb were de novo as well as transmitted mutations from asymptomatic/symptomatic parents. The RB1 mutation incidence was comparatively higher (25%) in nonfamilial Rb with emphasis on high prevalence in sporadic URB (18% versus 0%-9% in the literature series). The present studies demonstrated the efficacy of a multitechnique approach to detect various types of constitutional RB1 mutations such as RB1 deletion, deletion mosaicism, point mutation, mutation chimerism in patients of symptomatic/asymptomatic parents.

Base Sequence↗

Preliminary report of an intensified, short duration chemotherapy protocol for the treatment of pediatric non-Hodgkin's lymphoma in India.

BACKGROUND: In the past, the results of the treatment of non-Hodgkin's lymphomas (NHL) in Indian children have been poor, due to inadequate chemotherapy and poor supportive care. In an attempt to overcome these problems, we conducted a clinical trial in Bombay with a new protocol, MCP842. PATIENTS AND METHODS: Seventy-four previously untreated patients < 25 years were entered on study at the Tata Memorial Hospital, Bombay. Patients with lymphoblastic lymphoma (LL) (38) without bone marrow involvement and all patients with small noncleaved cell lymphoma (SNCL) (18) and large cell lymphoma (LCL) (18) were eligible. Treatment consisted of alternating cycles of two regimens, A and B. Patients with St. Jude stages I and II received six cycles, and those with stages III or IV received eight cycles. A cycles included cyclophosphamide, adriamycin, vincristine and ara-C, and B cycles, etoposide, vincristine, methotrexate, ifosfamide and mesna. RESULTS: Complete response was achieved in 67 (91%) of patients. Event free survival (EFS) for all patients was 58%; 68% for patients with SNCL and LCL combined, and 48% for patients with LL. There was no significant difference in EFS by histology (LL versus non-LL), or stage. There were nine (12%) toxic deaths, two during induction and seven in patients in remission; six occurred in patients with LL. CONCLUSIONS: These results are better than past results in Bombay. Unlike earlier CCG protocols, in which the outcome between patients with LL and non-LL differed, this was not so in MCP842. Even patients with extensive LL without bone marrow disease received only eight cycles of therapy, suggesting that short duration therapy is curative in as many as half of such patients--an important observation in a country with limited resources.

Adolescent↗

Survival of childhood acute lymphoblastic leukemia: results of therapy at Tata Memorial Hospital, Bombay, India.

The purpose of this study was to analyze the outcome of patients who completed therapy for acute lymphoblastic leukemia (ALL) and to study the role of an aggressive induction regimen in preventing post therapy relapses. Four hundred and twenty-two patients with ALL who completed therapy during the period 1975-1991 were followed. Two hundred and sixty patients received the aggressive MCP 841 protocol and 162 patients received various other less aggressive treatment regimens. Patients were followed with periodic examination and complete blood counts. The incidence of post therapy relapse was 27% in the less aggressive protocols and 15% in the MCP 841 protocol (p = 0.001). An higher percentage of relapses was seen in males (p = 0.05) and 89% relapses occurred within two years of stopping therapy. The relapse rate after 5 years of cessation of therapy was 0.59%. In conclusion, aggressive induction therapy is the most crucial factor in predicting relapses following cessation of therapy in ALL patients. However, relapses are unlikely to occur five years post therapy.

Adolescent↗

Low incidence of CNS relapse with cranial radiotherapy and intrathecal methotrexate in acute lymphoblastic leukemia.

OBJECTIVES: To assess the incidence of isolated central nervous system (CNS) relapses in patients of acute lymphoblastic leukemia (ALL) treated with a protocol containing cranial irradiation and intrathecal methotrexate as CNS directed therapy. DESIGN: Prospective non randomized study. SETTING: Department of Medical Oncology, Tata Memorial Hospital. SUBJECTS: 623 children of ALL on MCP 841. METHODS: CNS relapse was diagnosed, if upon examination of the CSF, more than 50 cells/microliter were observed, or a count of 5 cells which were unequivocally lymphoblasts. RESULTS: The incidence of isolated CNS relapse was 1.75% with the use of this treatment. Age, sex, white blood cell count, platelet count, lactic dehydrogenase and immunophenotyping were not significantly related to isolated CNS relapse. CONCLUSION: A low incidence of isolated CNS relapse demonstrates the adequacy of the presymptomatic CNS therapy.

Adolescent↗

Rapid cytoreduction in childhood leukemic hyperleukocytosis by conservative therapy.

Childhood leukemic hyperleukocytosis poses a serious threat to life because of its associated metabolic complications. The present prospective trial utilized conservative management of childhood acute lymphoblastic leukemia with hyperleukocytosis (total white cell count equal or > 100 x 10(9)/L) by intravenous hydration, urinary alkalinization, and allopurinol presenting without severe life-threatening complications. The median reduction in WBC count was 81.51% (range: 66-98.8%) within a median period of 36 hours (range: 12-60 hours) following hospitalization. There were no failures or treatment related complications. Thus we conclude that in childhood acute lymphoblastic leukemia, hyperleukocytosis can be managed safely and effectively with intravenous hydration, urinary alkalinization, and allopurinol before starting any specific anti-leukemic chemotherapy avoiding risk-associated cranial irradiation, leukapheresis, and exchange transfusion.

Adolescent↗

Pediatric germ cell tumor. An experience with BEP.

PURPOSE: This study is an analysis of our experience with bleomycin, etoposide, and cisplatin (BEP) chemotherapy, in pediatric germ cell tumors (GCTs). PATIENTS AND METHODS: The study included all children (age < 16 years) who were registered between May 1988 and May 1993 with a histologically confirmed diagnosis of GCT and received BEP chemotherapy. In addition to the clinicopathological features, the response rate, survival rate, and toxicity were analyzed. RESULTS: There was a total of 56 patients, of whom 22 had an ovarian tumor and 17 each had a testicular or an extragonadal tumor. Histologically, endodermal sinus tumor was the most common type (62%). Tumor markers were increased in 89% (50 of 56). Complete responses were observed in 89.1% (49 of 55) and partial responses in 10.9% (6 of 55) of the evaluable patients. Five-year actuarial survival was 83% and progression free survival was 93%. Median follow-up was 18 months. Median survival is not yet reached. The chemotherapy was well tolerated. CONCLUSIONS: From the present report, it is apparent that BEP chemotherapy is very effective and well tolerated in children with GCT. The data probably suggests that conservative surgery, when combined with effective chemotherapy, can result in cure of the majority of children with GCTs.

Adolescent↗

Evaluating efficiency of bone marrow harvest and its manipulation--role of CD 34 positivity.

We evaluated harvested marrow cells for total nucleated cells (27.49 x 10(9)), absolute 'lymphocyte' count (6.29 x 10(9)) and CD 34 positive cells (3.57 x 10(9)). The same parameters were studied after in vitro manipulation to remove RBCs and plasma. Reinfused WBCs contained 12.87 x 10(9) nucleated cells, 4.25 x 10(9) absolute 'lymphocyutes' and 3.34 x 10(9) CD 34 positive cells. The corresponding figures for loss during in vitro manipulation (tubing, RBCs and plasma) are 14.62 (53.18%), 2.04 (32.43%) and 0.23 x 10(9) (6.44%) cells respectively. Therefore CD 34 positivity may be a better indicator of total yield, loss during manipulation and reinfusion of hemopoietic progenitor cells in bone marrow transplantation.

Antigens, CD34↗

Malignant germ cell tumors in childhood.

The outlook for patients with germ cell tumors was poor before the advent of effective chemotherapy. In this study the outcome of multiagent chemotherapy in children treated for germ cell tumor is assessed. Between January 1984 and December 1990, 107 patients were diagnosed to have germ cell tumors. Postsurgical therapy was based on tumor site, stage, and histology. Combination chemotherapy was employed in patients with Stages I and II disease with postoperative raised tumor markers and all patients with Stages III and IV. Between 1984-1988, patients received cisplatin, vinblastin, bleomycin, and methotrexate (PVB-M), and thereafter between 1988-1990, they received bleomycin, etoposide, and cisplatin (BEP). Of 34 patients treated with PVB-M and 27 treated with BEP, the complete remission rate was 40% and 85%, respectively, and the overall survival was 30% at 5 years for PVB-M and 80% at 3 years for BEP. We conclude that etoposide with cisplatin is superior to vinblastin with cisplatin in the treatment of advanced germ cell tumors because of greater efficacy, decreased toxicity, and better compliance in children.

Adolescent↗

Pilot study of sequential combination chemotherapy in advanced and recurrent retinoblastoma.

Eight patients with advanced/recurrent retinoblastomas were treated with sequential combination chemotherapy incorporating cyclophosphamide, cisplatin, adriamycin, and etoposide. All patients achieved complete clinical response (CR) at the end of the first 75 day cycle. Three patients developed recurrence of which 2 patients had recurrence in the central nervous system and 1 patient had local recurrence. Median time to treatment failure was 30 weeks. Two patients succumbed to chemotherapy related neutropenic sepsis. One patient is alive and disease free for 72 weeks from start of treatment. This combination chemotherapy shows promise in patients with advanced/recurrent retinoblastoma and merits further study.

Antineoplastic Combined Chemotherapy Protocols↗

Brain tumors following cure of acute lymphoblastic leukemia.

The majority of children with acute lymphoblastic leukemia can be cured with effective modern day therapy. However, more and more long term sequelae including carcinogenic potential of the treatment are being recognised. We report two children who developed acute lymphoblastic leukemia at the age of 4 and 5 years respectively and were successfully treated. They developed meningioma and astrocytoma at 9 and 3 years respectively after completion of therapy. Both were treated surgically and the patient with astrocytoma also received radiotherapy. Both are now free of disease 19 months after diagnosis of second neoplasm.

Antineoplastic Combined Chemotherapy Protocols↗

131I-MIBG scintigraphy in neural crest tumours.

Radioiodinated meta-iodobenzylguanidine (131I-MIBG) has been widely used for the diagnosis of neuroblastomas, pheochromocytomas, paragangliomas and medullary carcinomas of thyroid. We have developed a procedure for preparation of 131I-MIBG and studied its utility in diagnosis of primary and metastatic neural crest tumours. Studies were carried out in 54 patients. Of them 39 cases were of neuroblastomas, 1 pheochromocytoma; 6 operated medullary carcinomas; 5 paragangliomas; 2 Ewing's sarcoma and 1 Rhabdomyosarcoma; The sensitivity for the detection of primary tumours of neuroblastomas was 94% and for the detection of metastasis was 83%; while in the case of paragangliomas and medullary carcinoma, the sensitivity was 75% and 70% respectively. Our experience in the present study shows that 131I-MIBG scintigraphy is a sensitive and specific diagnostic tool to localise primary and metastatic disease of neural crest tumours.

3-Iodobenzylguanidine↗

Adjuvant chemotherapy for osteogenic sarcoma of the extremity with sequential adriamycin and cisplatin.

Twenty-nine patients with high-grade nonmetastatic osteogenic sarcoma of the extremities were treated with adjuvant chemotherapy following definitive surgery. Chemotherapy consisted of systemic intravenous Adriamycin and cisplatin in a sequential fashion given for six courses. Nineteen out of 29 patients are alive and continuously disease free over a follow-up period ranging from 9+ to 30+ months. The relapse-free survival was 72%, and overall survival for the entire group was 69%. Median survival is not reached yet. Six out of 29 patients relapsed, of which 1 patient is alive for 6+ months after relapse. Three patients died of chemotherapy toxicity. The results were superior to historical controls treated with surgery alone. The need for more aggressive treatment approaches is discussed.

Adolescent↗

Ewing's sarcoma.

Between 1984-1987, 50 patients with Ewing's sarcoma of the bone were entered on combined modality protocol at Tata Memorial Hospital. Protocol treatment involved induction therapy consisting of 6-week therapy with vincristine, Adriamycin (doxorubicin), and cyclophosphamide (VDC) followed by local radiotherapy 50 Gy to the involved bone. This was followed for six more cycles of VDC. Five patients had metastatic disease at presentation. Seventy-six percent (38/50) of patients had disease either at axial or proximal site. With a median follow-up of 48 months (range 14-87) 21 patients remained alive with disease-free survival of 38.0% +/- 2.5% at 5 years and overall survival of 36.0% +/- 2.6% at 5 years. Twenty-five patients relapsed with five patients developing local failure and four local and distant metastasis. Using Lee-Desu statistical methods, only response to therapy was a significant factor for survival. We conclude that more aggressive therapy with proper selection of local treatment modality including surgery and/or radiotherapy is required to produce more long-term survival in high-risk Ewing's sarcoma.

Actuarial Analysis↗