Lyposomal Doxorubicin (Caelyx), Cyclophosphamide - Rituximab (DC-R) Plus GM-CSF as a Salvage Therapy in B-Diffuse Large Cell Lymphoma (B-DLCL) after Autologous Stem Cell Transplantation (ASCT) Failure.

B-DLCL patients after ASCT failure have a very poor prognosis, salvage chemotherapy or a second transplantation cannot substantially modify the very poor outcome which is characterized by a median overall survival (OS) of 3 months. We recently demonstrated the feasibility of chemoimmunotherapy after ASCT by associating a CHOP-modified schedule+Rituximab and GM-CSF, but often the antracycline retreatment in these patients can be hampered by the risk of severe cardiac damage or by a reduced organ reserve. For this reason we adopted a modified version of this protocol for patients receiving a previous Doxorubicin cumulative dose>300 mg/sm, with the substitution of conventional antracycline with a Lyposomal Pegylated Doxorubicin (DC-R schema); the other inclusion criteria were: diagnosis of B-DLCL CD20+, P.S (WHO)= 0–2, age < 75 years, relapse or progressive disease (PD) after ASCT, measurable disease, absence of severe organ dysfunction and CNS involvement. Seventeen patients were eligible for this salvage protocol; the median age was 47 (28–73) years; the P.S. (WHO) was 0–1 in 11 patients and 2 in six; the disease status after ASCT was: untested relapse in 14 cases and PD in 3 cases. The DC-R + GM-CSF schema (every three weeks) consisting in: R 375 mg/sm day 1 and 15, Caelyx 30 mg/sm and cyclophosphamide 750 mg/sm day 1, GM-CSF 150 mg/day from day 5 until neutrophils recovery. Patients showing disease progression after two courses were excluded while the responders received two more coursesof DC-R+GM-CSF; patients achieving complete remission (CR) after 4 courses did not receive any further treatment. All the17 patients received the planned treatment and were evaluable for response: the overall response rate (ORR) was 58.8% with 10 CR (58.8%), 7 patients showed a PD after 1–2 courses. The toxicity (WHO) consisted in: grade III–IV neutropenia in 11 patients (64.7%) and thrombocytopenia in 2 patients (23.5%), grade I–II infections in 2 patients and grade IV (pneumonia) in one patient. With a median follow up of 15 (1–74) months, 8 out of 10 responders patients are alive and in CR with a median disease-free survival of 24.5 (8–70) months, one patient is alive and in relapse at + 23 months and 1 patients died for infection months after while in CR. Our experience shows that DC-R + GM-CSF is an effective salvage treatment for B-DLCL after ASCT failure; indeed the follow up > 12 months in 5/17 (29.4%) patients in CR suggests a chance of cure.