Autologous Transplant for Therapy-Related Leukemia

Abstract & Commentary

By Andrew S. Artz, MD, Section of Hematology/Oncology, University of Chicago. Dr. Artz reports no financial relationship to this field of study.

Synopsis: This retrospective analysis from the European Transplant Registry summarizes the outcome after autologous transplant for 65 patients treated for t-MDS/AML. The cumulative incidence of relapse was 58% with a lower rate for patients in CR1 prior to transplant (CR1 vs non-CR1 at 3 years: 48 vs 89%; P = 0.05). The probability of 3-year overall and disease-free survival were 35% (95% CI, 21-49%) and 32% (95% CI, 18-45%), respectively. Improved outcome was seen in patients younger than 40 years and those transplanted in CR1. Although a small registry series, the data suggest autologous transplantation may be a reasonable option for young patients with therapy related MDS/AML in CR1, especially when no donor is identified.

Source: Kroger N, et al. Autologous stem cell transplantation for therapy-related acute myeloid leukemia and myelodysplastic syndrome. Bone Marrow Transplant. 2006;37:183-189.

Therapy-related myelodysplastic syndrome/acute myelogenous leukemia (t-MDS/AML) remains one of the most dreaded complications from chemotherapy and/or radiotherapy. The prognosis remains dismal, although a select group of patients with good risk cytogenetic abnormalities such as inv(16) or t(8;21) may have prolonged disease-free survival.1 However, for the vast majority of patients, disease control—and hence survival—is poor. Allogeneic transplant remains the standard treatment option2 if the patient can withstand such therapy and an appropriate HLA matched donor can be identified.2 Autologous HCT may be an alternative, although limited data have been reported for t-MDS/AML.

Between 1991 and 2000, 65 patients with t-MDS/AML who received autologous hematopoietic stem cell transplants (auto-HCT) were reported to the European Registry for Blood and Marrow Transplantation (EBMT). The median age was 39 years. After induction but before auto-HCT, 46 of the patients were in CR1, 8 in CR2, and 6 patients had refractory or relapsed disease. A non-TBI conditioning regimen was most commonly used.

Treatment-related mortality at 2 years was 12% (95% CI, 6%-38%). Univariate analyses showed lower TRM associated with younger age (< 40 years) (7% vs 47%; P = 0.007) and peripheral blood compared to bone marrow (5% vs 32%; P = 0.07) as the stem cell source. The 5-year cumulative incidence for relapse was 58% (95% CI, 44%-72%). Only remission status prior to auto-HCT (CR1 vs non-CR1) showed a lower relapse risk (48% vs 83%; P = 0.05). The 3-year disease-free survival (DFS) was 32% (95% CI, 18%-45%) with CR1 leading to enhanced DFS (41% vs 9%; P = 0.04). After adjusting, auto-HCT in CR1 (P = 0.006) and younger age (P = 0.02) resulted in superior DFS. The 3-year OS was 35% (95% CI, 21%-49%) with age younger than 40 years (P = 0.01) resulted in a superior OS. In multivariate analysis, OS was significantly better younger patients (HR, 1.03; 95% CI, 1.01-1.06; P = 0.008) and patients in CR1 prior to auto-HCT (P = 0.04).

The low rate of complete remission and overall poor outcome for t-MDS/AML has long been appreciated.3 This group of patients is a highly select subset who has therapy-related leukemia. This is demonstrated by low median age of 39 years, the high percentage of normal cytogenetics 14/34, and high percentage who achieved CR1 (71%). In a univariate analysis, younger age (< 40 years) was associated with a lower TRM (7% vs 47%; P = 0.007).

Commentary

The poor prognosis associated with t-MDS/AML presents a major treatment dilemma. In general, allogeneic transplantation is considered the optimal therapy. However, this is contingent on the ability to tolerate an allogeneic transplant and the availability of an HLA-matched donor. The poor response to initial induction and quick relapse rate represent another barrier to pursuing allogeneic transplant. Autologous transplant could be an alternative absent a HLA-matched donor, a not uncommon scenario.

In this retrospective review of 65 patients reported to the European Registry, the authors demonstrate a surprisingly good DFS at 3 years of 32%. The results appear even more promising considering the EBMT reported similar 3-year DFS of 35% for patients receiving an allogeneic HCT using an HLA-matched sibling for t-MDS/AML.4

But what inferences can we make from this registry analysis of a small number of patients? These patients clearly represent a highly select subset: the median age was 39 years, poor risk cytogenetics were infrequent, and 70% had achieved CR1 after induction. We clearly cannot compare other studies and conclude equivalence between auto-HCT and allogeneic HCT. However, the data suggest some patients may not only benefit, but potentially can be cured, despite t-MDS/AML. It may be reasonable for younger patients in remission with t-MDS/AML but no available HLA matched donor, to pursue consolidation with an autologous HCT.

References

1. Kern W, et al. Prognosis in therapy-related acute myeloid leukemia and impact of karyotype. J Clin Oncol. 2004;22:2510-2511.

2. Yakoub-Agha I, et al. Allogeneic bone marrow transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia: a long-term study of 70 patients-report of the French society of bone marrow transplantation. J Clin Oncol. 2000;18:963-971.

3. Michels SD, et al. Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases. Blood. 1985;65:1364-1372.

4. de Witte T, et al. Haematopoietic stem cell transplantation for patients with myelo-dysplastic syndromes and secondary acute myeloid leukaemias: a report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol. 2000;110:620-630.