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Single-Center Experience Indicates Relatively Good Prognosis After Allogeneic Stem Cell Transplantation Failure in CLL

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Key Points

  • The 2- and 5-year overall survival rates were 67% and 38% in patients with chronic lymphocytic leukemia with disease progression after allogeneic stem cell transplantation.
  • Among all patients, chronic graft-vs-host disease and initial response to stem cell transplantation were associated with improved survival.

In a retrospective single-center study reported in Journal of Clinical Oncology, Rozovski and colleagues found that chronic lymphocytic leukemia (CLL) patients with disease progression after allogeneic stem cell transplantation had a relatively good prognosis, with apparent benefit of salvage therapy. Better outcome was predicted by chronic graft-vs-host disease and initial response to allogeneic stem cell transplantation.

Study Details

The study involved 72 patients, consisting of 52 with CLL and 20 with Richter’s transformation, who underwent allogeneic stem cell transplantation between 1998 and 2011 at The University of Texas MD Anderson Cancer Center and had documented disease progression after transplantation. Of them, 22 (31%) never had a response to stem cell transplantation and 50 (69%) had a response and a relapse after a median of 7 months (range = 2–85 months). Patients who were receiving or were candidates to receive post-stem cell transplantation cell-based therapies were not included in the study.

The median age at the time of transplantation was 58 years (range = 30–72 years). Prior to stem cell transplantation 86% of patients received at least two treatment regimens, and 51% received at least three. Active disease was present in 92% at stem cell transplantation.

Post–Stem Cell Transplantation Treatments

Post–stem cell transplantation treatment included donor lymphocyte infusion in 44%. Among patients with CLL, 40% received rituximab (Rituxan), and 28% received ofatumumab (Arzerra); 13% received ibrutinib (Imbruvica; not available until 2010). Most patients with post–stem cell transplantation Richter’s transformation received chemoimmunotherapy with either hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine, or oxaliplatin, fludarabine, rituximab, and pegfilgrastim (Neulasta). Four patients with response to the first post-transplantation treatment regimen underwent a second allogeneic stem cell transplantation.

The response rate to first post-stem cell transplantation treatment was 45%, with complete response observed in three CLL patients and one with Richter’s transformation. Partial response was observed in 18 and 8 patients. Among 29 patients with failure of first-line post–stem cell transplantation treatment, 41% responded to subsequent treatments. Overall, patients received a median of two post–stem cell transplantation treatments (range = 0–8).

Survival

The 2- and 5-year overall survival rates were 67% and 38% in patients with CLL and 36% and 0% in patients with Richter’s transformation. Overall survival was better among patients who had acute graft-vs-host disease (median 45 vs 29 months, P = .04) and chronic graft-vs-host disease (median 37 vs 23 months, P = .05). On multivariate analysis, Richter’s transformation at transplantation (hazard ratio [HR] = 3.54, P < .001) and low hemoglobin at transplantation (HR = 0.76, P = .002, for higher vs lower) predicted poorer overall survival, and chronic graft-vs-host disease (HR = 0.53, P = .05) and initial response to stem cell transplantation (HR = 0.35, P = .004) predicted better overall survival.

The investigators concluded: “Patients with CLL in whom allogeneic [stem cell transplantation] fails may have a response to and benefit from salvage therapies, and their prognosis is relatively good.”

Zeev Estrov, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.

The study was supported by the Chronic Lymphocytic Leukemia Global Research Foundation and National Institutes of Health. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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