Suresh K. Pai

Consolidation Radiation After Complete Remission in Hodgkin's Disease Following Six Cycles of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine Chemotherapy: Is There a Need?

PURPOSE Combined modality treatment using multidrug chemotherapy (CTh) and radiotherapy (RT) is currently considered the standard of care in early stage Hodgkins disease. Its role in advanced stages, however, continues to be debated. This study was aimed at evaluating the role of consolidation radiation in patients achieving a complete remission after six cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy using event-free survival (EFS) and overall survival (OS) as primary end points. PATIENTS AND METHODS Two hundred and fifty-one patients with Hodgkins disease attending the lymphoma clinic at the Tata Memorial Hospital (Mumbai, India) from 1993 to 1996 received induction chemotherapy with six cycles of ABVD after initial staging evaluation. A total of 179 of 251 patients (71%) achieved a complete remission after six cycles of ABVD chemotherapy and constituted the randomized population. Patients were randomly assigned to receive either consolidation radiation or no further therapy. RESULTS With a median follow-up of 63 months, the 8-year EFS and OS in the CTh-alone arm were 76% and 89%, respectively, as compared with 88% and 100% in the CTh+RT arm (P =.01; P =.002). Addition of RT improved EFS and OS in patients with age < 15 years (P =.02; P =.04), B symptoms (P =.03; P =.006), advanced stage (P =.03; P =.006), and bulky disease (P =.04; P =.19). CONCLUSION Our study suggests that the addition of consolidation radiation helps improve the EFS and OS in patients achieving a complete remission after six cycles of ABVD chemotherapy, particularly in the younger age group and in patients with B symptoms and bulky and advanced disease.

NASOPHARYNGEAL CARCINOMA IN CHILDREN: COMPARISON OF CONVENTIONAL AND INTENSITY-MODULATED RADIOTHERAPY

PURPOSE To evaluate the efficacy of intensity-modulated radiotherapy (IMRT) in reducing the acute toxicities associated with conventional RT (CRT) in children with nasopharyngeal carcinoma. PATIENTS AND METHODS A total of 36 children with nonmetastatic nasopharyngeal carcinoma, treated at the Tata Memorial Hospital between June 2003 and December 2006, were included in this study. Of the 36 patients, 28 were boys and 8 were girls, with a median age of 14 years; 4 (11%) had Stage II and 10 (28%) Stage III disease at presentation. All patients had undifferentiated carcinoma and were treated with a combination of chemotherapy and RT. Of the 36 patients, 19 underwent IMRT and 17 underwent CRT. RESULTS After a median follow-up of 27 months, the 2-year locoregional control, disease-free, and overall survival rate was 76.5%, 60.6%, and 71.3%, respectively. A significant reduction in acute Grade 3 toxicities of the skin (p = 0.006), mucous membrane (p = 0.033), and pharynx (p = 0.035) was noted with the use of IMRT. The median time to the development of Grade 2 toxicity was delayed with IMRT (skin, 35 vs. 25 days, p = 0.016; mucous-membrane, 39 vs. 27 days, p = 0.002; and larynx, 50 vs. 28 days, p = 0.009). The duration of RT significantly influenced disease-free survival on multivariate analysis (RT duration >52 days, hazard ratio = 5.49, 95% confidence interval, 1.14-26.45, p = 0.034). The average mean dose to the first and second planning target volume was 71.8 Gy and 62.5 Gy with IMRT compared with 66.3 Gy (p = 0.001) and 64.4 Gy (p = 0.046) with CRT, respectively. CONCLUSION The results of our study have shown that IMRT significantly reduces and delays the onset of acute toxicity, resulting in improved tolerance and treatment compliance for children with nasopharyngeal carcinoma. Also, IMRT provided superior target coverage and normal tissue sparing compared with CRT.

Osteosarcoma of the head and neck region: Lessons learned from a single-institution experience of 50 patients

Osteosarcoma of the head and neck region is a rare tumor and is a therapeutic challenge because of its aggressive nature and complex anatomical location. Standard management guidelines are lacking due to paucity of published data.

L-asparaginase (Leunase) induced pancreatitis in childhood acute lymphoblastic leukemia.

A major complication of L-asparaginase therapy in acute lymphoblastic leukemia (ALL) is pancreatitis. Among the 915 cases of ALL seen over last 10 years, 19 (2%) developed pancreatitis. Median age was 5.5 years with a median duration of symptoms of 4 weeks. All cases had raised serum amylase and lipase. Pancreatitis was not related to the dose/duration of L-asparaginase therapy. Ultrasonography can be used as a corroborative investigation for diagnosis along with serum chemistries. Close clinical monitoring of children for early diagnosis of this complication is recommended.

Hepatitis B vaccination in acute lymphoblastic leukemia

Active immunization against hepatitis B virus infection was carried out in 162 patients with acute lymphoblastic leukemia attending the Outpatient Department at Tata Memorial Hospital. Recombinant DNA vaccine was given in three doses at 0, 1 and 2 months followed by a booster 1 year after the first dose. Antibodies to hepatitis B surface antigen could be detected in 19.7% of patients following vaccination. Of these only 10.5% had titers in the protective range. Immunosuppression induced by both disease and treatment appears to diminish responsiveness to vaccination. Passive active prophylaxis with both vaccine and immunoglobulin may be a more effective alternative in these patients.

Limb salvage surgery for osteosarcoma: effective low-cost treatment.

Successful management of osteosarcoma with limb salvage surgery is a challenging problem in the developing world. We report our early results with low-cost chemotherapy (without methotrexate) and low-cost limb salvage surgery. We prospectively collected data for 135 patients with histologically proven high-grade osteosarcoma of the extremities given neoadjuvant chemotherapy and treated with limb salvage surgery between January 2000 and February 2004. A locally designed and fabricated stainless steel customized megaprosthesis was used in 78 patients. Disease status and function was evaluated at followup ranging from 24 to 72 months. Followup data were available for 120 of the 135 patients. There were eight infections, four prosthesis breakages and three loosenings. Eighteen patients had local recurrence; 17 of these patients also developed lung metastases. Seventy-three patients (61%) were disease-free at followup. The group of 34 patients with 100% necrosis had better disease-free survival (79%). According to a modified Enneking system, the average functional score was 25.5 of 30 (85%) for the lower extremity and 20 of 30 (66%) for the shoulder. Our preliminary results suggest osteosarcoma can be managed well in a developing country in a cost-effective way. Limb salvage surgery has now become the standard of care.Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

Clinical significance of cytogenetic findings at diagnosis and in remission in childhood and adult acute lymphoblastic leukemia : Experience from India

We report cytogenetic findings in 114 patients of acute lymphoblastic leukemia (ALL), which includes 78 children (< or = 15 years) and 36 adults (16-60 years). Chromosome aberrations were detected in 109 (95%) cases. A lower frequency of hyperdiploidy (15%) in children and a higher frequency of hypodiploidy both in children (38.4%) and adults (44.4%) were found, in contrast to literature. Translocations were detected in one third of adult and pediatric cases. The incidence of t(9;22) was comparatively low in adults (7.7%). Frequency of t(1:19) was also low in overall ALL cases. Various other recurrent abnormalities such as del(6q), abn(11q23), i(9p), abn(12q13), del(7q), and i(17q) were seen in our cases; a striking difference in the incidence of del(6q) (41%) and abn(11q23) (30%) was found in our series versus reported literature. Ploidy distribution indicated association of pseudo- and hypodiploidy with B-lineage, and hypodiploidy with T-lineage in children. The occurrence of del(6q) was more frequent in pediatric ALL with highly aberrant pattern and also with lymphadenopathy. Abn(11q23) was found to be early-B and pre-B specific. Kaplan-Meier analysis of overall survival revealed prognostic value of sex, FAB, immunophenotype, and cytogenetic findings. Females and T-ALL patients had a better prognosis, whereas males and B-ALL patients had poor outcome in overall and pediatric age groups. Prognostic evaluation of cytogenetics indicated translocations as an independent high-risk predictor in childhood (P < 0.008) and adult ALL (P < 0.01). Childhood ALL with t(8;14) and t(4;11) and adults with t(9;22) had poor survival. Cytogenetics of remission marrows demonstrated disappearance of abnormal clones in 31.4%, and expansion in normal clones in 50% of patients. Persistence of original clones and development of new clones were observed in 20% and 33% of patients, respectively; whereas karyotype evolution was identified in 10% of patients. The prognostic significance of cytogenetic findings at diagnosis, and differential cytogenetic response in so-called clinical remission in our study indicated the utmost need for more intensive therapy for eradication of resistant clones, and necessity of sequential cytogenetic follow-up in these patients for identification of minimal residual disease.

Avascular Necrosis of Bone: A Complication of Aggressive Therapy for Acute Lymphoblastic Leukemia

The purpose of the present paper was to report cases of avascular necrosis of bone (AVNB) arising as a complication of chemotherapy for acute lymphoblastic leukemia (ALL). X-rays and 99mtechnicium-MDP bone scans were performed on patients with symptoms of bone pain, whereby five patients out of 850 patients were detected to have avascular necrosis of the femoral head. All had received aggressive chemotherapy with steroids. Two patients were still on therapy for the primary disease. In these patients further chemotherapy was continued without steroids. The median period from diagnosis of ALL to development of AVNB was 29 months. Three patients underwent corrective surgical procedures. To conclude, the data suggest that patients receiving combination chemotherapy, especially those with high cumulative doses, run a risk of developing AVNB. Awareness of this complication is important in order to have an early diagnosis so as to limit disability.

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.

Passive active prophylaxis against Hepatitis B in children with acute lymphoblastic leukemia

The aim of this study was to assess the antibody response to combined passive active immunisation versus active immunisation along with interferon against Hepatitis B in 60 patients with acute lymphoblastic leukemia (ALL) between 1 and 21 years of age with negative Hepatitis B virus (HBV) serology at presentation. Thirty-one patients received combined passive active immunisation with human specific Hepatitis B immunoglobulin (HEPABIG-VHB Pharmaceuticals) and Hepatitis B vaccine (arm I) and 29 patients received active immunisation along with interferon (arm II). Protective antibody levels were detected in 89.6 and 21% patients, respectively, at the 6-month evaluation. Infection with HBV occurred in 17 and 59% patients, respectively, at the 6-month evaluation. Interferon, thus, failed to serve the role as a vaccine adjuvant. At the 9-month evaluation of patients who received immunoglobulin, protective antibody titers were lost in 8 out of 19 evaluable patients (42%) and of these, 3 patients became HBsAg reactive at this point of time. This study indicated that 47.3% patients undergoing aggressive chemotherapy responded to combined passive active prophylaxis with protective titers of antiHBs at the 9-month evaluation. However, the rate of HBV infection was greatly reduced to 27%. We suggest that usage of passive immunisation in the aggressive phase, followed by active immunisation after cessation of intense chemotherapy would be a better option to increase the rates of protective antibody levels in these immunocompromised patients with leukemia.