Summary:Treatment options for patients with myeloma who relapse after allogeneic stem cell transplantation are limited. Thalidomide, an antineoplastic agent, has been shown to be effective in multiple myeloma through proposed mechanisms that may include angiogenesis inhibition. Herein we report successful thalidomide treatment of four patients who relapsed following allogeneic transplantation, three of whom had predominantly extramedullary relapse. Thalidomide was well tolerated in all patients; in two patients interferon-␣ was subsequently added to thalidomide as maintenance therapy without worsening graft-versus-host disease. We suggest that extramedullary myeloma is particularly sensitive to thalidomide, speculating that growth biology may in part be dependent on angiogenesis. Bone Marrow Transplantation (2001) 28, 1145-1150. Keywords: myeloma; thalidomide; transplantation; extramedullary; allogeneic; graft-versus-host disease Management options for multiple myeloma (MM) include autologous stem cell transplantation (autoSCT) and allogeneic bone marrow/stem cell transplantation (alloBMT). [1][2][3] Following alloBMT, a graft-versus-myeloma (GVM) effect is well recognized and may contribute to sustained molecular remission. 4-6 However, treatment options for relapse following alloBMT are often limited by concomitant graft-versus-host disease (GVHD), hematologic cytopenias or poor performance status.Thalidomide has antineoplastic properties, through proposed mechanisms that include angiogenesis inhibition, immunomodulation, apoptotic mechanisms, and modulation of T cell function. [7][8][9][10] In myeloma, angiogenesis as measured by microvessel density (MVD) has correlated with disease activity and outcome. [11][12][13] There is also recent evidence that thalidomide is active in vitro against MM cell lines resistant to standard chemotherapy. 14 Recently pub- lished studies have demonstrated activity of thalidomide in relapsed or refractory MM, 15-17 including patients who had had autoSCT. 18 To date there are no published data specifically examining the role of thalidomide for relapse after alloBMT.Trials investigating the role of interferon-␣ (IFN) in induction and maintenance phases of disease have yielded conflicting results. A recent meta-analysis demonstrated a survival advantage in this setting, suggesting that maintenance therapy may be of benefit. 19 We have concluded a clinical trial evaluating the efficacy of thalidomide, with IFN as maintenance treatment, in the management of relapsed or refractory MM. Four of the 75 patients accrued relapsed after HLA-identical sibling alloBMT. Herein we report successful thalidomide treatment in these four patients, three of whom had predominantly extramedullary (EM) relapse. Furthermore, we describe two of these patients who have proceeded to IFN maintenance therapy while on thalidomide. Issues related to EM relapse and the effects of the combination of thalidomide and IFN on disease control and GVHD are discussed. Study design of thalidomide trialPatients were pro...

A MTD was not reached. The regimen was tolerable, indicating that celecoxib can be safely administered with CRT for locally advanced OC.

The 4-day combination of dexamethasone, ifosfamide, cisplatin, and etoposide (DICE) is a salvage regimen for lymphoma. We report a prospective phase II multi-center trial of a modified DICE regimen in relapsed or refractory Hodgkin (HL) or non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), constituting a single day of intravenous administration followed by 3 days of oral administration, aimed at reducing inpatient days without losing efficacy. Forty patients (median age 56, range 25 - 79) were included: 28 (70%) NHL, 9 (23%) HL and 3 (8%) CLL. Fifty-three per cent had received 2 prior treatment regimens. International Prognostic Index (IPI) was 2 in 75% of NHL patients. Patients aged 55 and those with previous autologous stem cell transplantation (ASCT) started on a lower-dose regimen, with dose escalation possible in 2 patients. Overall response rate was 41%. Thirty-eight per cent of patients had stable disease. With a median of 3.1 years of follow-up, estimated progression-free survival (PFS) and overall survival (OS) rates at 3 years were 15% and 43% respectively. OS was longer in the < 55 compared to the 55 age cohort (P = 0.0091), longer for HL than NHL (P = 0.59 and 0.039 respectively) and longer for Low/Low-Int IPI than High/High-Int IPI (P = 0.0074 and 0.0009 respectively). Median duration of inpatient stay was 3 days. There were no treatment-related deaths. In conclusion, this modification of DICE is an effective and well tolerated salvage regimen, even in this poor prognosis group of patients. Further clinical studies of DICE in first relapse and in older patients, possibly with the addition of rituximab, are warranted.