report: Allo SCT for high-risk CLL

[Guest guest]

Retrospective study .... Just a reminder that we should also look also for

peer commentary on any published report. ~ Karl

==

Allogeneic Hematopoietic Stem-Cell Transplantation for Chronic Lymphocytic

Leukemia With 17p Deletion: A Retrospective European Group for Blood and

Marrow Transplantation Analysis

n = 44, majority of 17p deletions were detected via fluorescence in situ

hybridization analysis; the median percentage of deleted cells was 63%. 98%

had previously received fludarabine, more than half (60%) had

fludarabine-resistant disease. [AGE not specified in abstract] ..

participants had median of 3 previous lines of chemotherapy. One third of

the patients underwent an auto HSCT; half were not in remission at the time

of transplantation. [seems high risk to me]

When associated with a deletion of chromosome © 17p, chronic lymphocytic

leukemia (CLL) carries a poor prognosis because patients with this

abnormality typically do not respond to standard agents (ie, purine

analogs). The reason is that the p arm of c17 contains the p53 gene. Agents

that are p53 independent, such as alemtuzumab, induce higher response rates

but are still associated with dismal survival outcomes in these patients.

Thus, allogeneic hematopoietic stem-cell transplantation (HSCT) has been

proposed as an alternative treatment option.

Investigators of this cohort study evaluated progression-free survival and

overall survival after allogeneic HSCT in patients with CLL and a 17p

deletion.

A total of 44 eligible patients were identified from the European Group for

Blood and Marrow Transplantation database. The majority of 17p deletions

were detected via fluorescence in situ hybridization analysis; the median

percentage of deleted cells was 63%. Nearly all patients (98%) had

previously received fludarabine, and more than half (60%) had

fludarabine-resistant disease.

The patients had received a median of 3 previous lines of chemotherapy. One

third of the patients underwent an autologous HSCT; half were not in

remission at the time of transplantation. Of these 44 patients, 39 received

a reduced-intensity conditioning regimen. A similar percentage of patients

received stem cells from an HLA-matched sibling donor as from a matched,

unrelated donor.

Among patients who had measurable disease before undergoing transplantation,

42% achieved a complete response (CR) and 42% achieved a partial response

(PR).

The response rate increased to 94% in patients who had a PR at the time of

transplantation. At a median follow-up of 39 months, 16 patients sustained a

CR.

The 3-year overall survival and progression-free survival rates were 44%

and 37%, respectively.

Univariate analysis showed that ≥4 prior lines of chemotherapy, Binet stage

C, and use of alemtuzumab for T-cell depletion were poor prognostic markers.

The same relationships, however, were not upheld in the multivariate

analysis.

The results of this study showed that allogeneic HSCT was associated with a

significant survival benefit for patients with CLL and a 17p deletion.

Median survival with standard first-line therapy is only 1.5 years. However

the 3-year overall survival rate in this cohort was 44%.

A total of 9 patients remain in CR after >4 years of follow-up, with a

significant difference noted in relapse and progression rates when the

presence or absence of graft-vs-host disease (GVHD) is compared. Patients

with acute or chronic GVHD had a 0.2 relative risk of progression compared

with those without GVHD (P = .006).

The results of this study also suggest that allogeneic HSCT should be

considered early in the course of therapy for patients with CLL and 17p

deletion because patients receiving fewer prior lines of treatment exhibit

improved outcome.

J Clin Oncol. 2008 Nov 1;26(31):5094-5100, J Schetelig, A van Biezen, R

Brand, D Caballero, R o, M Itala, JA García-Marco, L Volin, N Schmitz,

R Schwerdtfeger, A Ganser, F Onida, B Mohr, S Stilgenbauer, M Bornhäuser, T

de Witte, P Dreger