Results of a randomized international study of high-risk central nervous system B non-Hodgkin lymphoma and B acute lymphoblastic leukemia in children and adolescents

Abstract

The prognosis for higher risk childhood B-cell non-Hodgkin lymphoma has improved over the past 20 years but the optimal intensity of treatment has yet to be determined. Children 21 years old or younger with newly diagnosed B-cell nonHodgkin lymphoma/B-cell acute lymphoblastic leukemia (B-NHL/B-ALL) with higher risk factors (bone marrow [BM] with or without CNS involvement) were randomized to standard intensity FrenchAmerican-British/Lymphoma Malignancy B (FAB/LMB) therapy or reduced intensity (reduced cytarabine plus etoposide and deletion of 3 maintenance courses M2, M3, M4). All patients with CNS disease had additional high-dose methotrexate (8 g/m 2 ) plus extra intrathecal therapy. Fifty-one percent had BM involvement, 20% had CNS involvement, and 29% had BM and CNS involvement. One hundred ninety patients were randomized. The probabilities of 4-year event-free survival (EFS) and survival (S) were 79% ؎ 2.7% and 82% ؎ 2.6%, respectively. In patients in remission after 3 cycles who were randomized to standard versus reducedintensity therapy, the 4-year EFS after randomization was 90% ؎ 3.1% versus 80% ؎ 4.2% (one-sided P ‫؍‬ .064) and S was 93% ؎ 2.7% versus 83% ؎ 4.0% (onesided P ‫؍‬ .032). Patients with either combined BM/CNS disease at diagnosis or poor response to cyclophosphamide, Oncovin [vincristine], prednisone (COP) reduction therapy had a significantly inferior EFS and S (P < .001). Standardintensity FAB/LMB therapy is recommended for children with high-risk B-NHL (B-ALL with or without CNS involvement).

Pediatric mature B-cell non Hodgkin lymphoma treatment with LMB-96 protocol. The Children Cancer Hospital Egypt experience

“…Mean age of the patients is slightly lower than many previous studies 5,12,14 , but similar to our previous report 15 . Age category below 4 years was the most common in the studied group in contrast to other study groups 13,16 , were ages between 5-9 years being the most common, although age is not considered as risk factor 17 . Cairo et al in 2012 identified advanced stage, increased LDH level > 2 X normal value, mediastinal disease and combined BM + /CNS + as the main risk factors for treatment response.…”

“…At last, 4 maintenance cycles, the first consisted of COPADM, followed by three cycles with low dose cytarabine and etoposide (cycles 2 and 4), with the third cycle being similar to the first but without HDMTX and IT. 13 …”

“…Patients in critical condition (renal failure, sepsis, grade III/IV organ toxicity) were allowed to receive a second course of COP prior to proceeding to induction. 13 …”

Stem cell transplantation for pediatric lymphoma: past, present and future

“…[10][11][12][13] The prognosis for advanced stage disease has also improved and varies based on subtype (60-90% 5-year EFS). 11,[13][14][15][16][17][18][19][20][21][22] HD Patients with HD commonly present with cervical or supraclavicular lymphadenopathy and most will present with some degree of mediastinal involvement. Current treatment involves the use of combined chemotherapy with or without low-dose involved field radiation therapy.…”

Safety and efficacy of intrathecal rituximab in children with B cell lymphoid CD20+ malignancies: An international retrospective study

“…It seems, however, that this therapy may also be useful as front line therapy for higher risk patients. Results of the FAB-96 study showed that the EFS was significantly lower in patients with mature B-NHL/ALL with isolated CNS involvement at diagnosis and even worse if the bone marrow was also positive, despite intensive systemic and intrathecal chemotherapy [3]. The efficacy and relatively low toxicity of IT and intraventricular rituximab suggests that this option could be considered in a future prospective front-line study for this group of patients.…”