Intensive short‐term chemotherapy regimen induces high remission rate (over 90%) and event‐free survival both in children and adult patients with advanced sporadic Burkitt lymphoma/leukemia

Abstract

The optimal treatment of advanced sporadic Burkitt lymphoma in adults is still a matter of debate. The salutary results of pediatric therapies did open the road for improving the adult outcome. Between May 1988 and March 2009, 71 consecutive patients-46 adults, 25 children-affected by Burkitt lymphoma/leukemia were treated with the same intensive pediatric protocol alternating vincristine, adriamycine and fractionated ciclophosphamide (phase A) with high dose methotrexate and high dose cytarabine (phase B) in four Italian institutions. Eighty-nine per cent of patients were in Stage III-IV or had L3 leukemia. Complete remissions were 67/71 (94.4%), 24/25 (96%) in children, and 43/46 (93.5%) in adults. Toxic deaths were 3/71 (4.2%), all in adults. There were nine relapses (one in children, eight in adults), all but one observed early. After a median observation of 94 months (range 23-275), the Event-Free Survival rate is 92% in children and 71.7% in adults (P 5 0.067). The 23 more recent adults received also rituximab, without differences in outcome as compared to patients who did not. Our experience confirms that such an intensive pediatric-derived chemotherapy is feasible and improves the long-term outcome of adults with advanced Burkitt lymphoma. Am. J. Hematol. 87:22-25, 2012. V V C 2011 Wiley Periodicals, Inc. IntroductionFifty years after its description [1] the optimal treatment of adult sporadic Burkitt lymphoma/leukemia (BL) still represents a matter of debate [2]. Standard chemotherapy such as CHOP [3] or adult ALL regimens [4] are clearly inadequate for treating BL, with a long term survival ranging from 0 to 30%. By contrast, the employment of intensive pediatric regimens in adult patients determined better results [5][6][7][8]. The HyperCVAD regimen, developed at the M.D. Anderson Cancer Center, confirmed a good activity in BL patients. However, the authors observed that patients older than 60 years clearly had an inferior outcome, with a survival rate of only 17% [9]. The addition of Rituximab and the improvement in supportive care measures possibly contributed to the achievement of similar outcomes in older and younger adults [10].In 1997, we reported a monocentric experience of 21 patients (8 adults and 13 children) treated with the intensive short-term pediatric-derived chemotherapy regimen POG 8617 [11], demonstrating that the outcome in adults was not significantly different than in children [12]. Fourteen years after our original report, we present here the longterm results of the same chemotherapy regimen employed in a multicenter experience recruiting a larger cohort of 71 consecutive BL patients. Of note, 48% of adult patients were older than 40 years and Rituximab was added to chemotherapy in the more recently enrolled adult patients. With a median follow-up of about 8.5 years, we confirm that this intensive pediatric-derived regimen is safe and improves the outcome of adults with advanced BL.

Rituximab is associated with improved survival in Burkitt lymphoma: a retrospective analysis from two US academic medical centers

“…Given that BL is CD20-positive, and extrapolating from the clear benefit of rituximab in DLBCL [Coiffier et al 2002;Pfreundschuh et al 2006], it is reasonable to hypothesize that rituximab might improve outcomes in BL. However, the existing literature is unclear in this regard, with three retrospective studies showing no significant improvement in outcomes with the addition of rituximab to doseintense regimens [Barnes et al 2011;Todeschini et al 2012;Wästerlid et al 2011] and one study showing a clear improvement in response rates, EFS and OS with rituximab among clinical trial CR, complete response; EFS, event-free survival; PFS, progression-free survival; OS, overall survival; HR, hazard ratio; NR, not reported; NS, not significant; BL, Burkitt lymphoma; B-ALL, acute lymphoblastic lymphoma; BLL, Burkitt-like lymphoma (B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and BL); DLBCL, diffuse large B-cell lymphoma with > 95% proliferation index); HyperCVAD, hyperfractionated cyclophosphamide, vincristine doxorubicin, and dexamethasone alternating with cycles of methotrexate and cytarabine; R-HyperCVAD, rituximab + HyperCVAD; R-HyperCVAD, rituximab + hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone); CODOX-M/IVAC, cyclophosphamide, vincristine, doxorubicin, methotrexate, ifosfamide, etoposide, ara-C; COPADM, cyclophosphamide, vincristine, prednisone, adriamycin, high-dose methotrexate; R-CODOX (Rituximab+CODOX); CHOEP, cyclophosphamide, doxorubicin, vincristine etoposide, prednisone; R-CHOP, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone.…”

“…High-intensity, brief duration regimens yield CR rates of 70-90%, and long-term event-free survival (EFS) rates between 45% and 97% [Evens et al 2013;Barnes et al 2011;Dunleavy et al 2011;Fayad et al 2007; Thomas et al 1999Thomas et al , 2006Rizzieri et al 2004;Mead et al 2002]. In contrast to other B-cell lymphomas, the impact of rituximab in combination with chemotherapy in BL is unclear, with some studies finding no benefit and others strongly Therapeutic Advances in Hematology 5 (1) suggestive of benefit [Wästerlid et al 2011[Wästerlid et al , 2013Todeschini et al 2012;Barnes et al 2011;Thomas et al 2006]. One randomized trial, presented in abstract form, reported an overall survival (OS) benefit of the addition rituximab to intensive chemotherapy [Ribrag et al 2012].…”

Trends in survival of patients with Burkitt lymphoma/leukemia in the USA: an analysis of 3691 cases

“…[1][2][3][4] More recent series and clinical trials report success rates in excess of 90% in pediatric 4,5 and 80% in adult populations. [6][7][8][9] The anti-CD20 monoclonal antibody rituximab has transformed the management of other mature B-cell malignancies. Because BL cells express abundant surface CD20, rituximab has been incorporated in multiple recent regimens reporting high success rates.…”

Oculomotor nerve palsy as a preceding symptom of adult sporadic Burkitt lymphoma: A case report and review of the literature

“…BL patients who received aggressive short-term chemotherapy demonstrated better overall survival rate than those who received chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisolone (also known as CHOP), which is routinely administered to patients with non-Hodgkin's lymphoma (23). Prophylactic cranial irradiation and prolonged maintenance have not demonstrated any proven benefits and are not currently recommended for treatment of the disease.…”