Treatment of B Non-Hodgkin's Lymphoma in children: the experience of multicentre studies and Brazilian National Cancer Institute's experience

Abstract

case each). The presence of bone involvement was observed in 23.7% of the patients and 3.9% presented CNS involvement. Time to diagnosis ranged from 1 to 210 days (mean = 47.1 days). The mean LDH was 2,014 U/mL (range 91U to 36,599U). 51 patients had immunephenotyping, 23 confirmed B (Burkitt´s) NHL, 13 T NHL patients, 2 T angiocentric NHL patients (one nasal e one testicular), 2 mediastinal diffuse large cell NHL patients (B), 4 abdominal diffuse large cell NHL patients (B), 7 large cell anaplastic lymphoma patients (T). 51 (67.1%) patients are alive and with no evidence of disease, 22 (28.9%) were dead, 2 (2.6%) alive (but with short followup) and 1 patient was lost of follow-up. The causes of deaths were: progressive disease (13; 59.1%), sepsis (7; 31.8%) and deep venous thrombosis and cardiogenic shock (1; 4.5% each). Pediatric lymphomas are the third most common neoplasm in children and adolescents. Unlike lymphomas in adults, childhood non-Hodgkin's lymphomas (NHL) are diffuse, aggressive neoplasms with a tendency to widespread dissemination. The outcome in childhood lymphoma non-Hodgkin's (NHL) has improved steadily over the past decade through the incremental development of multiagent chemotherapeutics regimens. At present, 80-90% of children are cured with intensive risk-adapted chemotherapy. The most recent era advance is chemotherapy directed toward both stage and histology, an approach that has been validated in randomized multicenter clinical trials. Nevertheless, in developing countries there are many obstacles to treatment of childhood lymphomas. The most important are late diagnosis, low socioeconomic status and under-nourishment . In developing countries patients with these conditions may be at increased risk for therapy-related toxicity, including life-threatening infections.In more recently trials, Patte et al. and Reiter et al., reported higher long term EFS in children with advanced stages of B-NHL using short intensive multiagent chemotherapy. However, the application of these regimens in developing countries may result in severe and life-threatening toxicity. Previously, our group reported 86.7% (SE=0.87) and 64% (SE=0.78) pEFS for children with early and advanced stage of non-lymphoblastic lymphoma, respectively. At that time, our results confirmed that a short duration therapy was effective to treat most children with non-lymphoblastic lymphoma in Brazil. Our following objective was to treat non-Hodgkin's B cell lymphoma in children with manageable toxicity-related morbidity without detriment of survival results. Between January 1998 to April 2003, 53 consecutive patients (age < 16 years), from National Cancer Institute, Brazil were stratified by risk factors (Stage and LDH level) and treated with BFM 86/90 (Berlin-Frankfurt-Münster) based protocol with reduction of metotrexate dose from 5 mg/m 2 to 2mg/m 2 . The mean age of patients was 6 years (range: 1 to 16 years). Seventy 2% of patients had lymphomas classified as Burkitt type; 11% as diffuse large cell lymphoma, 6% as Burkitt-like ...

Clinical characteristics and outcome analysis of pediatric B‐cell non‐Hodgkin's lymphoma. Experience with FAB‐LMB 96 and UKCCSG B‐cell NHL guidelines in a developing country

“…Surprisingly, baseline LDH failed to show any correlation with survival figures, as opposed to what other centers have observed, probably because of the fact that ours was a retrospective analysis and we could not gather this information in a significant minority of our patients, 1 although it is not a universal finding and there are examples in the international literature which do not favor high LDH as an adverse prognostic factor 2,7,17 . Our figures also do not suggest any relationship of baseline uric acid with TLS and its associated mortality but this may have been because of the missing values for some of our patients.…”

“…The patients in our study who died also showed an average time interval of only 35 days between diagnosis and death, with 21 deaths (46 percent) occurring within the first 30 days of starting treatment. This association of advanced disease with early death is well documented in the literature, where not just lymphomas but various other cancers have been shown to behave in a similar manner in this context 2,15 . The factors related to advanced presentation and hence poor outcomes in our study were the lack of health education among the general population, living far away from a health facility, delays in recognition of early signs of disease and poor health infrastructure.…”

“…Among pediatric non‐Hodgkin's lymphomas (NHL), B‐cell NHL constitutes the largest group. Unlike lymphomas in adults, childhood NHL are diffuse, aggressive neoplasms with a tendency to widespread dissemination 2 . The outcome of childhood NHL has improved remarkably over the past decade because of the development of risk‐adapted multi‐agent chemotherapeutic regimens, however, the situation is not always as encouraging in the developing world 3 .…”