Long Term Follow up of Allogeneic Hematopoietic Stem Cell Transplantation (ASCT) in Chronic Lymphocytic Leukemia (CLL).
Authors: Malhotra Pankaj , Hogan William J. , Litzow Mark R. , Elliott Michelle A. , Dispenzieri Angela , Call Timothy , Kay Neil E. , Zent Clive , Gastineau Dennis A. , Ansell Steven M. , Hayman Suzanne , Gertz Morie A. , Lacy Martha Q. , Porrata Luis F. , Inwards David J. , Tefferi Ayalew 
Published: October 2019

Background: Patients with CLL who relapse after prior fludarabine therapy have a poor prognosis with a median survival of 10 months [Keating MJ et al, Leuk Lymphoma 2002, 43:1755]. ASCT remains an effective salvage strategy for appropriately selected patients. We report long term follow up results on patients who have failed prior fludarabine therapy and subsequently underwent allogeneic transplantation for CLL.

Methods: A retrospective analysis of all patients who underwent ASCT from January 1997 until July 2004 at Mayo Clinic, Rochester was performed. All patients provided consent for research.

Patients: Thirteen patients (11 males) with B-CLL underwent 14 transplants. The median age was 43.5 years (range 18–55 years) and median time from diagnosis to transplant was 55 months (range 11–89 months). All patients had received prior fludarabine and ten had chemoresistant disease prior to transplant. The median number of chemotherapy regimens received prior to transplant was four (range 1–7). Five patients had cytogenetic abnormalities on bone marrow examination before transplant. Nine patients had extensive (>50%) involvement of bone marrow prior to transplant.

Results:

i. ASCT

A myeloablative conditioning regimen was used for 11 transplants, consisting of cyclophosphamide and total body irradiation (TBI) in nine patients, BEAC in one patient and TBI, thiotepa, cyclophosphamide and antithymocyte globulin in one patient who had a phenotypically partially matched related donor (8/10 match). One patient relapsed 43 months after myeloablative transplant and underwent a reduced intensity conditioning regimen (RIC) from the same donor. Three patients received a RIC regimen consisting of melphalan/fludarabine in two and fludarabine/TBI (200cGy) in one patient. Donors were matched siblings (n=9), phenotypically partially matched (8/10) family donor (n=1) or unrelated volunteers (n=3). Out of three unrelated donors, two donors were mismatched at one antigen. GVHD prophylaxis consisted of cyclosporin (CSA) and methotrexate (n=8), CSA and mycophenolate mofetil (n=2), CSA and prednisone (n=2) or CSA alone (n=1). The source of stem cells was bone marrow (n=11) and G-CSF stimulated peripheral blood (n=3). Median bone marrow mononuclear cell dose was 2.8 x108/kg and peripheral blood CD34+ dose was 8.15 x106/kg.

ii. GVHD and post-transplant course

Out of 13, 4 patients died within 2 months of transplant due to infections, one patient after 7 months due to infection (in remission) and one patient at 13 months due to relapse. Documented infections included bacterial (n=8), fungal (n=4) and viral infection (n=4). Acute GVHD (Grade II-IV) developed in 64.3% (9/14) and chronic GVHD in 35.7% (5/14) of transplant recipients. None of the patients required DLI. The median follow-up for surviving patients is 74 months (range 29 to 94 months). All seven surviving patients (including one patient who underwent second transplant) are currently in cytogenetic remission and have a Karnofsky performance score (KPS) of 90–100%.

Conclusion:

Allogeneic transplantation in young patients with CLL is an effective salvage strategy which can be associated with a high CR rate as well as a good quality of life for fludarabine refractory disease.