23
Extended Follow-up of Myeloablative, HLA-Matched Allogeneic BMT with High-Dose, Post-Transplantation Cyclophosphamide (PTCy) As Sole GVHD Prophylaxis: Favorable Outcomes Despite Low Incidence of Chronic GVHD

Track: BMT Tandem "Scientific" Meeting
Thursday, February 27, 2014, 4:45 PM-6:15 PM
Texas B (Gaylord Texan)
Christopher G. Kanakry, MD , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Hua-Ling Tsai, MS , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Javier Bolaņos-Meade, MD , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
B Douglas Smith, MD , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Ivana Gojo, MD , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Yvette L. Kasamon, MD , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Jennifer A. Kanakry, MD , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Marianna Zahurak, MS , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Ephraim Fuchs, MD , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Richard J. Jones, MD , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Leo Luznik, MD , Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Audio File Recorded Presentation
Introduction:  High-dose, PTCy is an effective strategy for GVHD prevention after allogeneic blood or marrow transplantation (alloBMT), but the impact of PTCy on long-term outcomes, particularly relapse, has not been assessed.  Here we report outcomes for 291 consecutive adult patients at Johns Hopkins treated with PTCy as sole GVHD prophylaxis.  

Methods:   All adult patients treated with this approach from its commencement in 2004 through 2011 were included.  Data were locked on June 30, 2013.  Median follow-up was 3.7 years (range 0.3-8.3) for surviving patients.  Allograft donors were HLA-matched-related for 60% and HLA-matched-unrelated for 40%.  All allografts were T cell replete and bone marrow derived in all but one who received peripheral blood stem cells.  Myeloablative conditioning (MAC) was busulfan(Bu)/Cy in 248 patients (85%), Bu/fludarabine in 42 (14%), and Cy/total body irradiation in 1 (0.3%).                                      

Median patient age was 49 years (range 18-66), and median HCT-CI score was 2 (range 0-12) with 39% having a score of ≥3.  At the time of transplant, 31% of patients were not in remission and an additional 28% had minimal residual disease.  Diseases included 138 AML (47%), 43 ALL (15%), 28 MDS (10%), 31 non-Hodgkin lymphomas (11%), 24 CML (8%), 13 Hodgkin lymphoma (4%), 9 multiple myeloma (3%), and 5 other diseases (2%).  High-risk disease characteristics of AML patients included adverse cytogenetics by the refined MRC criteria in 58 (42%), Flt3/ITD positivity in 37 (27%), and secondary from antecedent hematologic disorder in 51 (37%).  Forty-four percent of ALL patients were Philadelphia chromosome (Ph) positive. 

Results:   Primary graft failure occurred in 9 patients (3%).  By competing-risk analysis, the cumulative incidences (CI) of non-relapse mortality at 1 and 3 years were 17% and 18%, respectively.  Venocclusive disease occurred in 17 patients (6%) and was fatal in 4 patients (1%). 

The CIs of grades II-IV and III-IV acute GVHD were 44% and 14%, respectively, and acute GVHD was the cause of death in 6 patients (2%).  The CIs of grades III-IV acute GVHD were not different between matched-related or matched-unrelated alloBMT.  The total CI of chronic GVHD was 11% (8% for matched-related and 16% for matched-unrelated, p=0.03).

The CI of relapse at 3 years for all patients was 39% (37% AML, 33% ALL, 40% MDS).  The 3-year disease-free survival (DFS) probability for all patients was 42% (43% AML, 55% ALL, 53% MDS).  The 3-year overall survival (OS) probability for all patients was 58% (53% AML, 74% ALL, 67% MDS).  DFS and OS were similar regardless of donor relatedness.  A statistically significant impact of Flt3/ITD in AML or Ph+ in ALL on DFS or OS was not detected.

Conclusion:  The use of PTCy as sole GVHD prophylaxis after MAC HLA-matched alloBMT is associated with a favorable toxicity profile and affords long-term disease control for a large subset of patients with poor-risk hematologic malignancies in the absence of chronic GVHD.

Disclosures:
Nothing To Disclose
See more of: Oral Abstracts - Session D - Allogeneic Transplants
See more of: BMT Tandem "Scientific" Meeting
<< Previous Presentation | Next Presentation