Hyperfractionated cyclophosphamide with high‐doses of arabinosylcytosine and methotrexate (HyperCHiDAM Verona 897)

Abstract

BACKGROUND: Patients who have aggressive, refractory or recurrent non-Hodgkin lymphomas (NHLs) that are refractory to first-line anthracycline-containing regimens (ACRs) have a dismal outcome. Achieving complete remission (CR) is essential for a favorable outcome. To improve the CR rate in these patients, the authors designed a new protocol that contained hyperfractionated cyclophosphamide (CTX), high-dose arabinosylcytosine (HiDAC), and high-dose methotrexate (MTX) delivered sequentially in the same cycle and followed by the administration of granulocyte-colony stimulating factor (G-CSF) (HyperCHiDAM Verona 897). METHODS: Between February 1998 and May 2002, 28 consecutive adult patients (median age, 44 years) with aggressive NHL (B-lineage in 21%, T-lineage in 7%, and Ki-67 percentage > 50 in 82%) were entered on the protocol after they had failed on ACRs (15 patients with refractory disease, 6 patients with stable disease, 5 patients with recurrent disease, and 2 patients in partial remission). Patients characteristics were as follows: Twenty-two patients had Stage III-IV NHL (78.6%), 19 patients had B symptoms (67.8%), 22 patients had extranodal disease (78.6%), 12 patients had bulky mass (42.8%), 18 patients elevated lactate dehydrogenase levels (66%), and 8 patients had high-intermediate/high International Prognostic Index scores (64.3%). Patients received hyperfractionated CTX (300 mg/m(2)) and HiDAC (2 g/m(2)) every 12 hours on Days 2-4 and received high-dose MTX (400 mg/m(2) bolus plus 1600 mg/m(2) as a 24-hour continuous infusion on Day 1 with folinic rescue), followed by G-CSF. Subsequently, 15 patients underwent autologous stem cell transplantation (SCT), and 4 patients underwent allogeneic SCT. RESULTS: A CR was achieved by 18 of 28 patients (64.3%), a partial remission was achieved by 6 patients (21.4%), 4 patients were nonresponders or had progressive disease (14.3%), and there was 1 early toxic death (3.5%). Two of 18 patients developed recurrent disease (11.1%). The median follow-up for all patients was 35 months (range, from 2 months to > or = 74 months). Among the patients who achieved a continuous CR, the median follow-up was 48 months (range, from > or = 32 months to > or = 73 months). At the time of the current report, 13 of 28 patients (46.42%) were event-free. CONCLUSIONS: HyperCHiDAM Verona 897 was an effective regimen for patients with aggressive NHL who failed on ACRs, and it allowed patients to undergo subsequent SCT.