Tenali Gnana Sagar

Nonadherence to Imatinib adversely affects event free survival in chronic phase chronic myeloid leukemia

There is limited data on the impact of treatment interruptions due to nonadherence in patients with chronic phase chronic myeloid leukemia (CP‐CML) treated with Imatinib. We looked at factors (including adherence to therapy) affecting the outcome in a large cohort of patients with CP‐CML. All the 516 patients received Imatinib free‐of‐cost through a company sponsored scheme, which mandated regular three monthly visits for drug procurement. Data regarding the disease characteristics, adherence to treatment and outcomes, were obtained from patients records. Unwarranted interruption of treatment for more than 1 week was defined as nonadherence. With a median follow‐up of 39 months, the estimated 5‐year event free survival (EFS) was 70.8% (95%, CI = 63.3–78.3). Nearly one‐third of the patients (29.6%) were found to be nonadherent at some point during their treatment. On univariate analysis, the factors adversely affecting the EFS were prolonged symptom duration before diagnosis, treatment with hydroxyurea for more than 1 month before start of Imatinib, and nonadherence to therapy. Only nonadherence was significant in multivariate analysis (HR1.6; P = 0.048). The 5‐year EFS in adherent and nonadherent patients was 76.7% and 59.8% respectively (P = 0.011, log rank test). Nonadherent patients were less likely to achieve complete cytogenetic responses (26% versus 44%; P = 0.004; χ2 test) at any point. A significant proportion of patients with CP‐CML have drug interruptions due to nonadherence during therapy and this compromises the EFS. Adherence to therapy must be included as an important evaluation parameter in all future studies of CML. Am. J. Hematol. 2011.

Quality of life among younger women with breast cancer: study from a tertiary cancer institute in south India.

BACKGROUND The incidence of breast cancer in young patients less than 35 years is less than 1%. The physical and psychosocial morbidity may affect their ability to successfully function in their social roles. Hence we studied the quality of life (QOL) issues in this subset. MATERIALS AND METHODS Younger women with age less than 35 years, diagnosed with non-metastatic breast cancer at our Institute, from 1995 to 2005, were included in the study. Quality of life issues were studied during the follow-up using EORTC QOL C30 and BR23. Descriptive and inferential statistics were used in order to analyze the data. RESULTS A total of 51 patients were included for the study. The mean age at diagnosis was 30 years. The effect of breast cancer on the occupation and marital status was minimal. The global health status and the functional scores were high, while the overall sexual function was lower. The global health status was higher in the mastectomy group. The arm symptoms (P = 0.027) and pain were higher in the Breast conservation surgery (BCS) group. The sexual symptoms appeared to be higher in the ovary ablated group when compared to the ovary preserved group. The sexual functional scores (P = 0.02) and sexual enjoyment scores (P = 0.003) were better in the mastectomy group. CONCLUSION The overall QOL in younger patients with breast cancer appeared to be good. The QOL and sexual function were marginally worse in the breast conservation group when compared to mastectomy group.

Etoposide, cisplatin–etoposide, methotrexate, actinomycin-D as primary treatment for management of very-high-risk gestational trophoblastic neoplasia

To evaluate the efficacy of etoposide, cisplatin–etoposide, methotrexate, actinomycin‐D (EP–EMA) chemotherapy as the frontline treatment for gestational trophoblastic neoplasia (GTN) patients with very high (≥ 12) FIGO prognostic scores.

Preliminary experience with the use of bendamustine: a peculiar skin rash as the commonest side effect

BACKGROUND AND OBJECTIVES Bendamustine has been recently approved for the treatment of low-grade lymphoproliferative disorders. There is little data on the effectiveness or toxicity of this drug outside the trial setting. This is the first report on the use of bendamustine from the Indian subcontinent. SETTINGS AND DESIGN Retrospective descriptive analysis of response and side effects of bendamustine in eight patients with chronic lymphocytic leukemia and eight patients with follicular lymphoma. METHODS Data was collated from a review of case records. We examined any association between side effects and clinical parameters. RESULTS The median age of patients was 52 years and three-quarters had received prior treatment with alkylators or fludarabine. Three different protocols of bendamustine were used (single agent, in combination with rituximab or in combination with vincristine and prednisolone). The overall response rate was 80% (47% complete response, 33% partial response, and 20% progressive disease). The drug was well tolerated with very few grade 3/4 toxicities. More than half the patients (9/16) developed a characteristic erythematous, papular skin rash that resolved after completion of chemotherapy. CONCLUSION Bendamustine is a safe and useful addition to the drug arsenal against lymphoproliferative disorders. A peculiar skin rash was the commonest side effect noted in Indian patients treated with this drug.

Hypereosinophilia in hodgkin lymphoma

The incidence of eosinophilia in Hodgkin lymphoma is approximately 15%. Both peripheral and tissue eosinophilia have been noted in Hodgkin lymphoma. Eosinophils have important role in pathobiology of Hodgkin lymphoma. The mechanism of eosinophilia remains unknown though various mediators like IL-5 and GM-CSF have been implicated. We present a case who was diagnosed to have Hodgkin lymphoma and hypereosinophilia.

Voriconazole is a safe and effective anti-fungal prophylactic agent during induction therapy of acute myeloid leukemia

Background: Antifungal prophylaxis (AFP) reduces the incidence of invasive fungal infections (IFIs) during induction therapy of acute myeloid leukemia (AML). Posaconazole is considered the standard of care. Voriconazole, a generic cheaper alternative is a newer generation azole with broad anti-fungal activity. There is limited data on the use of voriconazole as a prophylactic drug. Materials and Methods: A single-center, prospective study was performed during which patients with AML undergoing induction chemotherapy received voriconazole as AFP (April 2012 to February 2014). Outcomes were compared with historical patients who received fluconazole as AFP (January 2011-March 2012, n = 66). Results: Seventy-five patients with AML (median age: 17 years [range: 1-75]; male:female 1.6:1) received voriconazole as AFP. The incidence of proven/probable/possible (ppp) IFI was 6.6% (5/75). Voriconazole and fluconazole cohorts were well-matched with respect to baseline characteristics. Voriconazole (when compared to fluconazole) reduced the incidence of pppIFI (5/75, 6.6% vs. 19/66, 29%; P < 0.001), need to start therapeutic (empiric + pppIFI) antifungals (26/75, 34% vs. 51/66, 48%; P < 0.001) and delayed the start of therapeutic antifungals in those who needed it (day 16 vs. day 10; P < 0.001). Mortality due to IFI was also reduced with the use of voriconazole (1/75, 1.3% vs. 6/66, 9%; P = 0.0507), but this was not significant. Three patients discontinued voriconazole due to side-effects. Conclusion: Voriconazole is an effective and safe oral agent for IFI prophylaxis during induction therapy of AML. Availability of generic equivalents makes this a more economical alternative to posaconazole.

Late effects of treatment in survivors of childhood cancer from a tertiary cancer center in South India.

Background: Improved survival after childhood cancer is attributed to intensive, aggressive therapy, adverse sequelae of which can manifest months to years after completion of treatment. There is little information about the late adverse effects of both childhood cancer and its therapy in survivors in India. Aim: To determine the long-term sequelae associated with therapy in childhood cancer survivors attending a tertiary cancer center in India. Materials and Methods: We studied 155 consecutive survivors of childhood cancer who were ≤14 years at the time of diagnosis and had completed 3 years of follow-up. The study included a complete history and clinical examination, with specific investigations to detect organ toxicity. Quality of life (QOL) was assessed from responses to a standardized questionnaire. Neurocognitive assessment was carried out in 20 survivors with an adaptation of the revised Wechsler adult intelligence scale for adults and the Malins intelligence scale for children. Results: The late effects included impaired fertility in 38 patients (24.5%), impaired growth pattern in 7 (4.5%), endocrine dysfunction in 7 (4.5%) and second malignancy in 2 (1.2%). Three of the 20 patients assessed had severe neurocognitive impairment. A high QOL was reported by 60% of survivors and an “average” QOL by 38%. Conclusion: Our study showed that most survivors had a good QOL and our results will help clinicians to better monitor childhood cancer survivors in countries with limited resources.

Voriconazole-induced pancreatitis in a patient of acute myeloid leukemia and invasive aspergillosis.

To the Editor: A 16-year-old girl (30 kg) was diagnosed with intermediate-risk acute myeloid leukemia and induced with daunorubicin 60mg/m for 3 days and cytarabine 100mg/m for 7 days. On day 8, she developed febrile neutropenia, with sinusitis and persistent cough. Computerized tomography revealed nodular infiltrates in lungs with perilesional haloes and mucosal thickening of the maxillary sinuses with mass in the nasal cavity. A histologic examination of the nasal mass showed filamentous fungi suggesting invasive aspergillosis. She had earlier been started on empiric antibiotics (imipenem+cilastatin and vancomycin) and amphotericin B deoxycholate (1mg/ kg/d). The culture of the fungal specimen revealed Aspergillus flavus resistant to amphotericin B, intermediate to itraconazole, and highly sensitive to voriconazole. She was started on oral voriconazole (300mg bd on day 1 followed by 200mg bd). She showed improvement in respiratory function and reduction in facial edema within 48 hours. There was no hepatic or renal dysfunction before or after starting voriconazole, and she tolerated the drug well except for transient visual hallucinations. Twelve days after starting voriconazle, she developed severe epigastric pain unresponsive to pantoprazole. Serum amylase was elevated (234 IU/mL) and computerized tomography showed pancreatitis. The neutrophils had recovered and the infection was resolving. Azole-associated pancreatitis was considered and voriconazole was stopped. The pancreatitis was managed conservatively and the patient improved. Amylase normalized within 12 days. She was in remission, and considering proven aspergillosis, there was a need for continued antifungals during consolidation using high-dose cytarabine. As the isolate was resistant to amphotericin B and caspofungin was unaffordable, voriconazole was reintroduced at 100mg bd as prophylaxis. She tolerated it well and had an uneventful course. On the day 15 of the second high-dose cytarabine course, she developed epigastric pain and vomiting. Serum amylase was elevated (637U/mL). Medication review showed that the patient was wrongly taking a dose of 200mg bd of voriconazole in the 1 week before the episode. Voriconazole was stopped and she improved with conservative management. The third course of cytarabine was uneventfully delivered without antifungal prophylaxis. Eight months after completion of therapy, she remains in remission and has had no recurrence of abdominal problems. Pancreatitis has been reported as a complication of azole use.1,2 Although other drugs including cytarabine have been implicated in the causation of pancreatitis,3 the temporal relationships noted above and the nonoccurrence of the event when cytarabine was used without azoles in the third cycle strongly point toward voriconazole as the culprit in our patient. Passier et al2 described 4 patients with itraconazole-induced pancreatitis and 42 other cases have been mentioned. The mechanism of azole-induced pancreatitis is not clear and may be idiosyncratic considering the poor predictability and low incidence. The drug literature of voriconazole mentions pancreatitis as a side effect in pediatric patients, but there are no reports in the English literature.4 Although it may be idiosyncratic, the occurrence in pediatric patients may suggest dose dependence. In our patient, pancreatitis occurred only when a higher dose of the drug was used (7mg/kg/dose) and not otherwise. We can only conjecture on the ways to avoid this side effect. Meticulous attention to doses in pediatric patients and drug level monitoring whenever such facilities are available maybe of help.5,6 Intravenous administration of voriconazole may be less toxic to the gastrointestinal tract.7 Pancreatitis is a serious toxicity of voriconazole in pediatric patients and must be kept in mind as the use of this drug is expanding.

Hepatoblastoma: Analysis of treatment outcome from a tertiary care center

Aim: This study was designed to retrospectively review our experience with the multimodality management of hepatoblastomas (HB). Materials and Methods: Thirteen patients were treated for HB between 2000 and 2007. The clinical presentations, chemotherapy tolerance and response, surgical procedure undertaken, and complications were analysed. Results: Median age of the population was 12 months (3-60 months), with a male-to-female ratio of 3.3:1. Nine patients were treated with neoadjuvant chemotherapy incorporating cisplatin and adriamycin. Primary surgery was done in four patients. Extent of hepatic resection in the operated patients varied. Mixed type was the predominant histopathological diagnosis. Adjuvant chemotherapy was well tolerated with no morbidity or mortality. Five-year event-free survival (EFS) and overall survival (OS) of all the 13 patients is 76.9%. All the nine patients who could complete multimodality treatment are alive with no evidence of disease or complications with median follow-up of 63 months (46-122 months). Conclusions: Treatment of HB with multidisciplinary approach was well tolerated. OS and EFS of patients were comparable with published studies.

Acute lymphoblastic leukemia: A single center experience with Berlin, Frankfurt, and Munster-95 protocol.

Background: There is a paucity of data on the outcome following the treatment for acute lymphoblastic leukemia (ALL) from developing countries. Materials and Methods: Two hundred and thirty-eight consecutive patients with ALL <30 years of age diagnosed between January 2005 and December 2011 were analyzed retrospectively. Patients were treated modified Berlin, Frankfurt, and Munster 95 protocol. Event-free survival (EFS) was calculated using Kaplan-Meier survival analysis and variables were compared using log-rank test. Results: The EFS was 63.4% at a median follow-up was 32.7 months. On univariate analysis National Cancer Institute (NCI) risk stratification, sex, white blood cell count, day 8 blast clearance, and income were significantly associated with EFS. However, on multivariate analysis only female sex (P = 0.01) and day 8 blast clearance (P = 0.006) were significantly associated with EFS. Seventy-four of 238 (31%) patients had recurrent leukemia. The common sites of relapse were bone marrow in 55/74 (75%) patients and central nervous system in 11/74 (20%) patients. Conclusion: Compared to western data, there was an increased proportion of NCI high-risk patients and T-cell immunophenotype in our study. There has been an improvement in outcome of patients with ALL at our center over the last 2 decades. Female sex and clearance of blast in peripheral blood by day 8 of induction was associated with better EFS.