Rejiv Rajendranath

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.

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.

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.

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.

Spontaneous regression of primary progressive Hodgkin's lymphoma in a pediatric patient: a case report and review of literature.

Spontaneous regression of malignancies is a very rare phenomenon. Our research of existing literature yielded only 16 cases of Hodgkins lymphoma which regressed spontaneously. The outcome of primary progressive Hodgkins lymphoma is poor even with salvage chemotherapy and autologous bone marrow transplantation. Here we present a case of primary progressive Hodgkins lymphoma, which regressed spontaneously after failure of salvage chemotherapy. To our knowledge, this is the first case report of primary progressive Hodgkins lymphoma undergoing spontaneous regression.

Malignant ectomesenchymoma of the nasal cavity

Malignant ectomesenchymomas are rare tumors. This tumor affects predominantly young children. Most common site is head and neck. A multi modality approach should be appropriate for this soft-tissue tumor. We present a 43 year old female with malignant ectomesenchymoma of the nasal cavity.

Early CNS toxicity after intrathecal methotrexate

Central nervous system (CNS) being a sanctuary site, intrathecal methotrexate (IT MTX) has become a cornerstone for CNS prophylaxis for acute lymphoblastic leukemia. Recently we noticed eight pediatric patients developing transient neurological event following IT MTX. All of them were acute lymphoblastic leukemia (ALL) patients. Four were high risk patients and others were standard risk (based on total count and age). All of them received BFM 86 protocol. Seven were females. Their age ranged from 4–14 years and the median age was 11.5 years. All the patients had normal CSF studies. Five of them received IT MTX along with intravenous high dose MTX (HDMTX) 5 gm/m before the event. Two received cytosine arabinoside (AraC), (75 mg/m for 4 days) with IT MTX on day one. Only one received cranial irradiation before the event. All the patients developed the event between Day 11 to D14 of IT MTX. Seven patients had hemiparesis and one had quadriparesis. The neurological event recovered within 24 hours in seven of them and within 72 hours on the others. Cerebrospinal fl uid (CSF) study was normal in all patients. All of them were exposed to multiple doses of IT MTX prior to the event. Preservative free MTX recommended dosage (12 mg) was used for all patients and proper administration technique under sterile precautions was ensured. Imaging studies were conducted in all patients within 24 hours of the onset of the event and all had normal standard MR imaging study of the brain. The imaging studies were not repeated later. The incidence of various neurological events following IT-MTX is estimated around 4–15% [1]. Three distinct clinical patterns of neurotoxicity have been observed (a) an acute toxicity, occurring within hours of IT chemotherapy, probably resulting from chemical arachnoiditis; (b) sub acute toxicity occurring within days or weeks, and characterized by symptoms of seizures, transient paresis, or cerebellar abnormalities; and (c) a delayed leukoencephalopathy form that is more commonly observed when IT MTX is used with cranial irradiation [1]. The mechanism of methotrexate induced neurotoxicity is poorly understood. Both high-dose intravenous MTX and intrathecal MTX are proposed to have association with demyelination, white matter necrosis, loss of oligodendroglia, axonal swelling, microcystic encephalomalacia, and atrophy relatively selective for the deep cerebral white matter [2]. An altered myelin metabolism disturbance induced by S. Cyriac · T. G. Sagar · R. Rajendranath Department of Medical Oncology, Cancer Institute, 18 Sardar Patel Road, Guindy, Chennai 600 036, India

Immediate treatment effects of high-dose methotrexate and cranial irradiation on neuropsychological functions of children treated for acute lymphoblastic leukemia at a regional cancer center.

Context: Overall cure rates for pediatric acute lymphoblastic leukemia (ALL) have improved; however, the neuropsychological sequelae of ALL treatment have not been adequately documented in India. Aims: The present study assesses the immediate effects of ALL treatment on neuropsychological functioning, at the Regional Cancer Center in Chennai, South India. Materials and Methods: Newly diagnosed with ALL patients (n = 24) (aged 6–15 years; 13M:11F) registered between March 2008 and February 2009 were included. Patients who had received high-dose methotrexate (HD-MTX) and cranial radiotherapy (CRT) as part of their treatment were enrolled for the study. Neurocognitive assessments were done to assess various functions such as performance intelligence, visuo-perception, visuo-spatial, perceptual organization, processing speed, planning, working memory, and immediate verbal memory (IVM) (Malins intelligence scale); verbal fluency (ideation fluency test) and verbal attention (vigilance test). Three assessments were done during induction (baseline), after re-induction phase (second) and during the maintenance phase (third). Results: The patients performed significantly worse in the third assessment (mean duration from diagnosis 17.48 months) on performance intelligence quotient (PIQ), visuo-perception, visuo-spatial, processing speed, planning, IVM, verbal attention, and verbal fluency (P < 0.05), there were no significant changes observed in visuo-perceptual organization and working memory (P > 0.05). Significant difference was observed between age groups 6 and 10 (41.7%) and 11–15 years (58.3%) in perceptual organization, verbal fluency, and verbal attention (P < 0.05) and no gender difference was observed across the three assessments (P > 0.05). Conclusions: Combining HD MTX and CRT had an immediate effect on neuropsychological sequelae among the children with ALL, however, long-term evaluation is recommended to study the long-term effects.