Hyper-CVAD is effective therapy for adult ALL [

Kantarjian et al, JCO 18:547, 2000
;
Kantarjian et al, Cancer 101:2788, 2004
]. Intensive chemotherapy with hyper-CVAD (fractionated cyclophosphamide, vincristine [VCR], doxorubicin and dexamethasone) was alternated with high dose methotrexate and cytarabine every 21 days for 8 courses with G-CSF and prophylactic antibiotics, followed by maintenance with POMP (6-MP, methotrexate, VCR, prednisone). Complete response (CR) rate was 92% with 3-year disease-free survival (DFS) rates 38% overall. A modified hyper-CVAD regimen was developed to address the following: (1) higher induction mortality in patients (pts) aged 60 or older (17% versus 3%); (2) longer DFS reported with early anthracycline intensification; (3) worse survival with CD20 expression (excluding Burkitt’s [BL] and lymphoblastic lymphoma [LL] subtypes); (4) CNS relapse rate of 6% and 1% in low and high risk pts, respectively and (5) late relapses after completion of therapy.

Modifications to Hyper-CVAD

ParameterHyper-CVADModified Hyper-CVAD
Laminar air flow rooms No For age ≥ 60 yrs or poor PS 
Dose-intensive anthracycline No C2 Liposomal DNR & cytarabine 
Rituximab No For CD20 ≥ 20 
Intrathecal treatments 4–16 6–8 
Maintenance (POMP) 2 years 3 years 
Intensifications (MTX, asparaginase) Months 7 & 11 Months 6,7 & 18,19 with hyper-CVAD 
ParameterHyper-CVADModified Hyper-CVAD
Laminar air flow rooms No For age ≥ 60 yrs or poor PS 
Dose-intensive anthracycline No C2 Liposomal DNR & cytarabine 
Rituximab No For CD20 ≥ 20 
Intrathecal treatments 4–16 6–8 
Maintenance (POMP) 2 years 3 years 
Intensifications (MTX, asparaginase) Months 7 & 11 Months 6,7 & 18,19 with hyper-CVAD 
View Large

Newly diagnosed or primary refractory (1 course only) pts were eligible. BL and Ph+ ALL pts were excluded. From May 2000 to December 2001, 77 pts were treated with the modified regimen detailed above (9 courses of intensive chemotherapy). The program was then modified further with elimination of course 2 anthracycline intensification. An additional 80 pts were treated with hyper-CVAD with or without rituximab (8 courses of intensive chemotherapy). The median age for these 157 pts was 40 yrs (range, 15–83) with 20% aged ≥ 60 yrs; 57% were males. Overall response rate was 94% in the evaluable pts (8 too early) with no difference by CD20 expression (49% were CD20+). No induction deaths were observed in the elderly subgroup (2 younger pts with induction deaths). Outcome with anthracycline intensification appeared worse, particularly in the CD20 negative group. The addition of rituximab appeared to improve DFS in CD20 positive group (with or without anthracycline intensification) compared with hyper-CVAD alone (2 yr DFS 90% versus 65%, p=.03); however, overall survival in the CD20 positive group was influenced by deaths in CR (10%) in elderly patients related to GNR sepsis or pneumonia during the intensive phase. Additional accrual and follow-up is needed to further define the role of rituximab in non-Burkitt’s adult ALL.

Topics:
acute lymphocytic leukemia, hypercvad protocol, rituximab, brachial plexus neuritis, liposomes, cd20 antigens, anthracycline antibiotics, chemotherapy regimen, cytarabine, methotrexate
2005, The American Society of Hematology
2005
Sign in via your Institution