Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP)

Abstract

Ninety patients with progressive recurrent lymphoma were treated with a combination of cisplatin 100 mg/m2 intravenously (IV) by continuous infusion over 24 hours, followed by cytosine arabinoside in two pulses each at a dose of 2 g/m2 given 12 hours apart. Dexamethasone, 40 mg orally or IV, was given on days 1 through 4. Vigorous hydration was reinforced by routine use of mannitol. Treatments were repeated at 3- to 4-week intervals for six to ten courses. Most patients had not achieved complete remission (CR) with prior therapies, which included Adriamycin (all patients) and methotrexate and VP-16 (58 patients). Median patient age was 55 years. Intermediate-grade lymphoma was the most frequent pathologic diagnosis. Seven patients died within two weeks of therapy; of the remaining 83 patients, 28 (34%) or 31% if all patients are considered, achieved CR, and 22 (26.5%) achieved partial remission (PR). Response was evident after the first two cycles of chemotherapy and appeared to be independent of the histopathologic type of lymphoma. To date, only eight of the complete responders have relapsed at a median follow-up of 11 months. The overall 2-year survival in 25%. Further analysis showed that patients with low tumor burden and normal lactic acid dehydrogenase (LDH) had a high CR response rate (67%) and a survival rate of 61% at 2 years. In contrast, patients with both high tumor burden and elevated serum LDH levels had a negligible CR rate, and only 5% are surviving at 1 year. Patients with either high tumor burden with normal LDH or low tumor burden with elevated LDH had an intermediate survival. Myelosuppression-related infection was the most frequent serious complication of this regimen (31%) and the cause of death of ten patients. Acute lysis syndrome was also observed in five patients with high tumor burden and was the cause of death in three of these patients. DHAP has proven to be an effective non-crossresistant regimen for patients with relapsing or refractory lymphoma, particularly for patients who have favorable prognostic characteristics.

Autologous peripheral blood stem cell transplantation in patients with relapsed lymphoma results in accelerated haematopoietic reconstitution, improved quality of life and cost reduction compared with bone marrow transplantation: the Hovon 22 study

“…The results obtained using the DHAP±VIM regimen do not seem to differ from studies using either DHAP or VIM, although in the present study more non-cross-resistant chemotherapeutic agents were used (Velasquez et al, 1988;Herbrecht et al, 1991). The major reason for discontinuation of chemotherapy in the present study was progressive/ non-responsive disease in 40±50% of the patients before high-dose chemotherapy could be given.…”

“…Various chemotherapy regimens have been described for patients with progressive recurrent lymphoma. Extensive experience has been obtained with the DHAP (cisplatin, cytarabine, dexamethasone) regimen prior to myeloblative chemotherapy (Velasquez et al, 1988;Philip et al, 1991). Around 40±60% of patients obtain a partial or complete response and therefore prove to be chemo-sensitive.…”

Dose escalation therapy in previously untreated patients with multiple myeloma following Z‐Dex induction treatment

“…PBSC were mobilized using DHAP chemotherapy, as previously described (Velasquez et al, 1988). Intensive preand post-hydration was given in conjunction with cisplatin, including forced diuresis with i.v.…”

“…DHAP is a regime that is extremely efficacious in highgrade lymphoma (Velasquez et al, 1988) and may also have direct disease-modifying activity in myeloma by targeting the proliferating fraction, irrespective of how this is conceptually defined. Although this remains unproven, in vitro studies demonstrate that cisplatin targets proliferating myeloma cells (Ghanta et al, 1977;Barlogie et al, 1989) and Ara-C is likely to be effective in cells which express nucleoside transporter complexes in high numbers.…”

Autotransplants for histologically transformed follicular non‐Hodgkin's lymphoma

“…Patients were eligible for autotransplant at the time of transformation or after subsequent relapse(s), provided that chemosensitivity to a salvage regimen could be demonstrated. Patients who had not previously received an anthracycline were treated with CHOP (cyclophosphamise, hydroxydoxorubicin, vincristine and prednisone) (McKelvey et al, 1976) as salvage whereas those who had been treated with CHOP before transformation received DHAP (high-dose cytarabine, cisplatin and dexamethasone (Velasquez et al, 1988) or mini-BEAM (carmustine, etoposide, cytarabine and melphalan) (Girouard et al, 1997). Prior therapy for low-grade lymphoma was unrestricted in the type and number of regimens.…”