In Multiple Myeloma (MM) CAMPATH-1 Antibodies “In the Bag” Reduce the Early Toxicity of Stem Cell Transplantation from Graft vs. Host Disease (GvHD) and Seem To Be Associated with Improved Long Term Outcome.

Introduction: Although allogeneic stem cell transplantation remains the only curative approach in patients with MM, its role remains controversial. Early high treatment related mortality, particularly from infections, GvHD and later, from disease recurrence remains substantial challenges. This study reviewed the outcome of consecutive patients who received T-cell depleted grafts from HLA identical siblings.

Patients and Methods: Patients with symptomatic MM (stage II, n= 4 & III, n=17) who had an HLA identical sibling were initially treated until response with anthracycline or steroid based combinations. Three patients had, in addition, undergone autografting. Individuals who received cytokine mobilized peripheral blood progenitor cell (PBPC) grafts were also prescribed therapeutic serum levels of cyclosporine for 90 days post transplantation. The objective of the study was to determine transplant related mortality OS and DFS.

Results: Twenty one patients with a median age of 44 (range 37– 56) years who had responded to chemotherapy (CR or VGPR) received stem cell enriched grafts from HLA identical siblings. Median performance status was 1 (0 – 2). Five individuals had significant organ dysfunction from effects of the disease. At presentation median albumin and β2MG blood levels were 30 g/L and 3.2 ng/mL, respectively. Myeloablative conditioning was radiotherapy (n= 12) or chemotherapy (n= 9) based. GvHD prophylaxis consisted of T-cell depletion with CAMPATH-1G (n=7) or H (n=14) antibodies “in the bag”. BM had all been treated with ex vivo with CAMPATH-1G (median 20 mg) while PBPC grafts in 14 patients were incubated with CAMPATH-1H (median 10 mg). Patients received a median of 23 ×10⁴/kg CFU-GM in 0.87 BM mononuclear cells or 9.22 ×10⁸/kg PBPC (CD34+: 4.46 ×10⁶/kg). Median time to engraftment was 12 days. Two patients developed GvHD (grade 2) and 3 limited chronic form (1 progressed from acute). The 1 year non relapse mortality was 19%. Six patients suffered disease recurrence. One refused further therapy. Three of 5 responded to DLI and 2 remain in unsustained remission. Fatal events appeared lower in patients receiving chemotherapy based conditioning (mortality 11% vs. 50; p= 0.06), exposure of stem cells to CAMPATH-1H (15% vs. 62.5%; p= 0.04) and a lower median CAMPATH-1 dose given (p= 0.01). Cox analysis confirmed that lower CAMPATH-1 dose was associated with improved outcome. Fourteen (67%) patients survive at a median of 1101 days (range 385–5309) and 62% are disease free.

Conclusions: In this cohort of chemotherapy responsive patients with advanced myeloma, ex vivo T-cell depletion of allogeneic grafts was associated with good protection from GvHD and 19% 1-year transplant related mortality. Low grades of GvHD post transplantation were associated with a favourable impact in the long term survival.