Abstract

Background: Non-Hodgkin's lymphoma (NHL) is an aggressive malignancy. Its outcome has improved over the past decades. Although it accounts for 8%–10% of all childhood cancers, very less information about its clinical presentation and outcomes is available from India. Our objective was to study the clinical presentation and outcomes in children (<15 class="b" xss=removed>Methodology: We retrospectively analyzed 26 children diagnosed with NHL at our center from August 2008 to June 2014 and followed them up to May 2017. Results: The median age at the time of diagnosis was 7.7 years (2.5–13 years). Abdominal distension and an abdominal lump were the most common presenting features occurring in 75%, followed by fever (73.8%) and weight loss (46.2%). Most patients had advanced-stage (Stage III/IV, 92.3%) disease at presentation. The primary presentation was extranodal in 57.7%, nodal in 26.9%, and combined in 15.4%. Burkitt's lymphoma (BL) was the most common subtype (46.2%), followed by T-lymphoblastic lymphoma, diffuse large B-cell lymphoma, and anaplastic large-cell lymphoma. Three patients did not take treatment. The median follow-up of patients was 48 months (36–99 months). Nineteen patients achieved remission and four had progressive disease. Significantly better event-free survival (EFS) was found with younger age and lower stage of presentation. The EFS did not significantly differ with sex, group of disease, lactate dehydrogenase levels, and presenting features. Conclusions: Our cohort of patients with NHL showed characteristics similar to those reported from other developing countries. NHL occurred at a younger age, with a higher incidence of BL. The outcome for patients aged >10 years was poor. The outcome of NHL was comparable to that of other centers in the world.

Introduction

Malignant lymphomas (including non -Hodgkin's lymphoma [NHL] and HL) are the third most common group of malignancies in children after leukemias and brain tumors. They account for 15% of all childhood malignancies in children younger than 20 years.[1] Approximately 60% of pediatric lymphomas are NHL, whereas the rest are HL.[2]

Most NHLs in children present as an aggressive disseminated disease. Potential clinical emergencies in patients with NHL prior to diagnosis are superior/inferior vena cava obstruction, acute airway obstruction, spinal cord compression, pericardial tamponade, intussusception/intestinal obstruction, and central nervous system (CNS) complications. The outcome of childhood NHL has improved progressively over the past decade to about 80%–90% with intensive risk-adapted multiagent therapy.[3],[4],[5]

In developing countries, there are many obstacles to the treatment of childhood lymphomas. The most important are late diagnosis, low socioeconomic status, and poor nutrition.[6],[7],[8] The lack of awareness at primary care level, universal health-care provision, and poor socioeconomic status lead to late presentations with advanced stage disease, thus influencing outcomes.

There is a scarcity of data on the clinical profile and outcomes of treatment of childhood NHL in India. Here, we present the experience in the management of childhood NHL from a single tertiary center in a large metropolitan urban setting, focusing specifically on the clinical profile and outcome of these children.

Methodology

Eligibility, staging, and diagnosis

The data of children younger than 15 years diagnosed with NHL at the All India Institute of Medical Sciences, New Delhi, diagnosed with NHL over 6 years from August 2008 to June 2014, were retrospectively analyzed. The study was approved by our Institutional Ethics Committee. Twenty-six patients who had been diagnosed with NHL during this period were identified, and data regarding clinical features, diagnostic and staging workup, and treatment outcomes were collected.

The workup for all patients included a detailed history; physical examination; standard blood tests including lactate dehydrogenase (LDH); computed tomography (CT) scan of the primary site along with neck, chest, abdomen, and pelvis; and bone marrow (BM) aspiration and biopsy. NHL was staged according to St Jude/Murphy staging system[9] before treatment initiation.

The diagnosis was on the basis of either ultrasound or CT-guided core needle or excisional biopsy. The presence of neoplastic cells in the cerebrospinal fluid and the clinical sign of CNS involvement defined CNS disease. To evaluate malnutrition, the Z-scores were used for each patient's weight for age (undernutrition), height for age (stunting), and weight for height (wasting) (WHO Z-scores in children <5 href="https://www.thieme-connect.com/products/ejournals/html/10.4103/ijmpo.ijmpo_70_18#JR_10" xss=removed>10] and Indian Academy of Pediatrics Z-scores in children >5 years of age).[11]

Stratification

Therapy was stratified into three risk groups[3] according to the following criteria: risk Group 1 (R1) was defined as patients having lymphoma with initial complete resection; risk Group 2 (R2) was defined as patients diagnosed with lymphoma with no or incomplete resection and involvement of only extra-abdominal sites and LDH level <500>

Treatment

The patients were stratified by risk factors (stage and LDH level) and treated with the NHL-Berlin–Frankfurt–Münster (BFM 90) protocol.[3],[12] At diagnosis, all patients were treated with vigorous hydration and allopurinol to prevent tumor lysis syndrome (TLS). All patients received a cytoreductive phase with prednisone and cyclophosphamide. After the 5th day of prephase, the first course of chemotherapy was initiated the next day depending on the condition of the patient. In our patients' group, no one was in Group R1. Patients in Group R2 received four courses of multiagent chemotherapy (AA-BB-AA-BB). Patients in Group R3 received six courses, i.e., AA-BB-AA-BB-AA-BB. Conditions for starting the subsequent course of therapy were as follows: platelets >100,000/μL and neutrophils >1000/μL after the nadir of postchemotherapeutic cytopenia. The minimal interval between the two successive courses was at least 4 weeks.

Patients in risk groups R2 and R3 who had a residual tumor after two therapy courses received therapy course CC. Patients were re-evaluated after course CC. If no viable lymphoma tissue was found, therapy was continued with three more courses (AA-BB-CC).

Patients of lymphoblastic lymphoma (LBL) were treated with the International Network for Cancer Treatment and Research (INCTR), an unpublished study protocol for LBL/lymphoma and the MCP 841 protocol.

Response evaluation

Physical examination of all clinically documented sites of disease was performed prior to the initiation of each cycle. All patients underwent a CT scan of the neck, chest, and abdomen upfront. A CT or positron emission tomography (PET) scan study was performed after the first two cycles of chemotherapy. Follow-up evaluations included history, physical examination, and laboratory examinations every 3 months during the 1st year after the end of the therapy and at 4–6-month intervals during the following 3 years and yearly thereafter. PET or CT scans were performed when clinically indicated. Progression was defined as a recurrence of tumor documented by clinical examination, X-rays, ultrasound, and CT scan or PET scan studies. Patients with initial BM and CNS involvement were evaluated with punctures of BM and CNS until clearing of blasts. Complete response was defined as the complete disappearance of clinical and radiological lesions. Disease progression was defined as increase by ≥25% of at least one measurable lesion, or by the appearance of a new lesion. Event-free survival (EFS) was determined as the time from the initiation of treatment to progression, death, or the most recent follow-up examination.

Statistical analysis

Data were statistically described as frequencies (number of cases) and percentages where appropriate. Descriptive statistics were used to calculate the relative frequencies of age, sex, histopathologic types, and clinical and laboratory features. Survival curves were plotted using the Kaplan–Meier method, and comparison was made using the log-rank test. P < 0>

Results

Patient characteristics and presentation

There were 26 patients of NHL who were treated at our center during the above period. The median age at the time of diagnosis was 7.7 years (2.5–13 years). There were 21 males. The presenting clinical characteristics of patients are shown in [Table 1]. The abdominal distension/lump was the most common presenting feature occurring in twenty patients (76.9%), followed by fever (73.1%), weight loss (46.2%), breathlessness (34.6%), pallor (34.6%), lymphadenopathy (26.9%), and bone pain (19.2%). The physical/radiological findings of the cohort are shown in [Table 2]. An abdominal mass (69.2%) was the most common finding. Pleural effusion was present in 46% of patients and about 19% of the patients presented with a superior mediastinum syndrome/superior vena cava syndrome.