Hyper-CVAD Program in Burkitt's-Type Adult Acute Lymphoblastic Leukemia

Thomas, Deborah A.; Cortes, Jorge; O’Brien, Susan; Pierce, Sherry; Faderl, Stefan; Albitar, Mäher; Hagemeister, Frederick; Cabanillas, Fernando; Murphy, Samuel G.; Keating, Michael J.; Kantarjian, Hagop M.

doi:10.1200/jco.1999.17.8.2461

Cited by 241 publications

(175 citation statements)

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“…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].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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“…First line chemotherapy regimens include CODOX-M plus IVAC, hyper-CVAD, or dose adjusted EPOCH [21–23]. …”

Section: Discussionmentioning

confidence: 99%

Multiple cranial nerve palsies in immunodeficiency subtype of Burkitt lymphoma

Ali

Kalla

2018

Journal of Community Hospital Internal Medicine Perspectives

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Burkitt lymphoma is a late complication of HIV, and bilateral cranial nerve palsies are extremely rare in patients with AIDS. A twenty year old Caucasian male with known congenital HIV who had been non-adherent with anti-retroviral therapy presented with multiple cranial nerve palsies and was eventually diagnosed with Burkitt lymphoma. Before chemotherapy, he was started on radiation therapy to the brain, meninges, and base of skull with the intent of improving cranial nerve palsies and preventing further neurological sequelae since the cranial nerve palsies were dense and there was concern that intrathecal chemotherapy would have less penetration than radiation. He eventually died due to overall disease burden. We hereby present what we believe is the first reported case of Burkitt lymphoma presenting with bilateral facial, vestibulocochlear, left abducens, and mandibular nerve palsies. Recognition of different presentations of Burkitt lymphoma is extremely important as it would aid in early diagnosis and initiation of both chemotherapy and anti-retroviral therapy potentially leading to improved outcomes.

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“…This limits our ability to assess the risk of PH in patients with HS and ongoing hemolysis (albeit extravascular). Also from this study we cannot conclude that PH in HS does not occur at an increased frequency over the general population since idiopathic PH is extremely rare (estimated prevalence less than 0.2%) [25,26] and thus a prohibitively large number of HS patients would be required to power such a study. However, given the upper 95% confidence interval of 12% prevalence of PH for the splenectomized participants in our current study, it does not appear that splenectomy in HS confers a similar risk for PH as in thalassemia.…”

Section: Prevalence Of Pulmonary Hypertension In Hereditary Spherocytmentioning

confidence: 92%

“…However, patients at high risk with resistant disease are mostly older and comorbid, thus SCT often is not practicable. Furthermore, if patients do not respond to initial, intensive therapy, further course of disease is often fatal [25,26]. In our cohort, no patient received high dose therapy with autologous or allogeneic SCT in first remission, but autologous SCT was part of salvage-therapy in two patients.…”

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confidence: 98%

“…As CNS relapse appears in approximately 30% to 50% [24] if CNS prophylaxis is not given, intrathecal prophylaxis has become standard. Thomas et al [25] found routine radiotherapy not to be necessary and reserved cranial radiation for specific cases (e.g., cranial nerve root palsies), as the majority of patients can undergo effective prophylaxis or treatment with intrathecal chemotherapy. Thereby CNS failures can be reduced to 3-5%.…”

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confidence: 99%

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In situ follicular lymphoma associated with overt B‐ or T‐cell lymphomas in the same lymph node

Carbone¹,

Libera²,

Zannier³

et al. 2011

American J Hematol

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There have been several attempts to improve treatment and outcome of patients with primary mediastinal B-cell lymphoma (PMBL) and Burkitt's lymphoma (BL). In recent years, chemotherapy dose intensification and the addition of rituximab have led to a remarkable progress and have developed into integral parts of treatment for both entities of lymphoma [1][2][3][4]. Here, we report our monocenter results of a highdose methotrexate based alternating regimen with rituximab (B-ALL/ NHL 2002 protocol) in 15 patients with PMBL and 28 patients with sporadic BL. Since the early 1980s, protocols of GMALL have been continuously adapted and in the meantime they have become reference treatment for BL and B-ALL in Germany. The latest changes comprised the additional use of rituximab, standardized G-CSF support, implementation of high-dose cytarabine, intrathecal triple therapy, and age-adjusted stratification. Furthermore, we additionally amended supportive care with palifermin as it reduced severity and prevalence of mucositis [5].Almost all patients responded to chemotherapy, leading to an overall response rate of 98% (PMBL 100%, 95% confidence interval (CI) 1.0-1.0; BL 96.4%, 95%CI 0.68-1.0). Complete remission (CR) was achieved in 83.8% (PMBL 80%, BL 85.7%), and the rate of partial remission (PR) was 14% (20% PMBL, BL 10.7%). On average, the individual best response to chemotherapy was achieved after 3.68 courses.After initial response, three patients (two BL, one PMBL) experienced a progression or relapse within 3, 5, and 10 months, respectively. Thus, 5-year progression-free survival (PFS) was 93.3% (95%CI 0.74-1.0) for patients with PMBL and 82.1% (95%CI 0.67-0.96) for BL. Five-year overall survival (OS) was 100% for PMBL and 94.1% (95%CI 0.83-1.0) for BL in the younger group, and 100% and 63.6% (95%CI 0.35-0.92), respectively, in patients >55 years (Fig. 1a,b). Regarding the BL group, two patients died from treatment-related sepsis, a 74-year-old woman discontinued therapy, and two progressed during salvage therapy.Postchemotherapy consolidation radiotherapy was performed in 66.7% in PMBL and in 10.7% in BL. A total of 93% of patients with PMBL and 100% of patients with BL received prophylactic intrathecal therapy.Overall response and survival rate of 100% of all patients in the PMBL subgroup was observed. Fietz et al. [6] already reported a CR rate of 73% and an OS of 80% at 8.6 years in a cohort of 15 patients with PMBL treated according a prior B-ALL protocol of the GMALL (without rituximab). Improved OS in our cohort may be explained by recent changes such as the additional use of rituximab or high-dose cytarabine. Additional use of rituximab had predominantly shown benefit in nonmethotrexate but not in methotrexate-containing regimens [3,4,[7][8][9]. Preliminary results of a current protocol by Hoelzer et al. [10] with 42 patients with PMBL showed an inferior CR rate of 69%, but a comparable 3-year OS of 90% in patients younger than 55 years and of 67% in the elderly group (>55 years). However, this difference c...

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Hyper-CVAD Program in Burkitt's-Type Adult Acute Lymphoblastic Leukemia

Abstract: Hyper-CVAD is effective in adult B-ALL. Identification of patients with high risk for relapse and improved methods to detect residual disease may result in risk-oriented approaches.

Cited by 241 publications

References 26 publications

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

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

Multiple cranial nerve palsies in immunodeficiency subtype of Burkitt lymphoma

In situ follicular lymphoma associated with overt B‐ or T‐cell lymphomas in the same lymph node

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