Long term outcome of Hyper-CVAD-R for Burkitt leukemia/lymphoma and high-grade B-cell lymphoma: focus on CNS relapse

Abstract

Burkitt leukemia/lymphoma (BL) and high-grade B-cell lymphoma (HGBL) have a high incidence of central nervous system (CNS) involvement, which is associated with poor prognosis. The Hyper-CVAD-R regimen includes systemic and intrathecal CNS-directed therapy to treat and prevent CNS disease. We report herein the long-term safety and efficacy of the Hyper-CVAD-R regimen in adults with BL and HGBL, focusing on its efficacy to prevent CNS relapse. Among 79 adults (54 BL, 25 HGBL), the median age was 44 years (25% ≥ 60 years old), 73% had bone marrow (BM) involvement and 28% had CNS involvement. The complete remission rate was 91% (BL 96%; HGBCL 79%; p=0.16). The 5-year relapse-free survival (RFS) and overall survival (OS) rates were 58% and 52%, respectively. The cumulative incidence of relapse (CIR) was 21% (BL 14%; HGBCL 37%, p=0.06) and was associated with baseline BM (27% vs 0%; p=0.02) and CNS (42% vs 12%; p<0.01) involvement. In multivariate analyses, age and CNS involvement were independent predictors for OS and RFS. The 5-year CNS CIR was 6% (BL 4%; HGBL 11%, p=0.31); 16% with baseline CNS involvement (p=0.03). Our data support the use of Hyper-CVAD-R in preventing CNS relapse, especially among high-risk patients with BM or CNS involvement.

The evolution of acute lymphoblastic leukemia research and therapy at MD Anderson over four decades

“…In patients 40 years and younger, Hyper-CVAD therapy was more favorable than other regimens such as CODOX-M/IVAC (cyclophosphamide, doxorubicin, high-dose methotrexate/ ifosfamide, etoposide, and high-dose cytarabine) and DA-EPOCH-R. However, in patients 60 years and older, Hyper-CVAD was associated with more toxicities [88,89]. Patients with CNS disease and marrow involvement had less favorable outcomes and may require an intensive approach such as Hyper-CVAD.…”

Burkitt Lymphoma Presenting as Ileocolic Intussusception in an Adult

“…Ultimately, combination chemoimmunotherapy remains the standard-of-care for adults with BL. One of three regimens is recommended for first-line therapy: 1) R-CODOX-M alternating with IVAC; 2) R-hyper CVAD (rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone typically alongside high-dose methotrexate and cytarabine); or 3) DA-EPO-CH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab) [ 41 ] [ 42 ] [ 43 ] [ 44 ]. Patients with high-risk disease, bone marrow involvement, or CNS disease require high-intensity regimens, such as R-CODOX-M/IVAC (as in our patient) or R-hyper CVAD [ 42 ] [ 44 ].…”

“…One of three regimens is recommended for first-line therapy: 1) R-CODOX-M alternating with IVAC; 2) R-hyper CVAD (rituximab with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone typically alongside high-dose methotrexate and cytarabine); or 3) DA-EPO-CH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab) [ 41 ] [ 42 ] [ 43 ] [ 44 ]. Patients with high-risk disease, bone marrow involvement, or CNS disease require high-intensity regimens, such as R-CODOX-M/IVAC (as in our patient) or R-hyper CVAD [ 42 ] [ 44 ]. Otherwise, a risk-adapted approach using DA-R-EPOCH is suitable for patients without CNS disease, as recent data suggests similar efficacy to R-CODOX-M/IVAC but with lower treatment-related toxicity [ 45 ].…”

Intravascular large B-cell lymphoma masquerading as stroke successfully treated with R-Hyper-CVAD

“…The patient underwent a partial nephrectomy performed for a right renal mass ultimately diagnosed as concurrent oncocytoma and IVLBCL. This was treated with standard R-Hyper-CVAD that included intrathecal methotrexate and cytarabine ( Appendix for treatment protocols) [7] . Complete remission was achieved and has been maintained for 5 years following diagnosis.…”