Background
In older patients with acute myeloid leukemia (AML), the definition of fitness, prognosis, and risk of death represents an open question.
Methods
In the present study, we tested the impact ...on survival of disease‐ and patient‐related parameters in a large cohort of elderly AML patients homogeneously assigned to treatment with hypomethylating agents (HMAs).
Results
In 131 patients with a median age of 76 years, we confirmed that early response (<0.001) and biology‐based risk classification (p = 0.003) can select patients with better‐predicted survival. However, a full disease‐oriented model had limitations in stratifying our patients, prompting us to investigate the impact of baseline comorbidities on overall survival basing on a comorbidity score. The albumin level (p = 0.001) and the presence of lung disease (p = 0.013) had a single‐variable impact on prognosis. The baseline comorbidity burden was a powerful predictor of patients' frailty, correlating with increased incidence of adverse events, especially infections, and predicted overall survival (p < 0.001).
Conclusion
The comorbidity burden may contribute to impact prognosis in addition to disease biology. While the therapeutic armamentarium of elderly AML is improving, a comprehensive approach that combines AML biology with tailored interventions to patients' frailty is likely to fully exploit the anti‐leukemia potential of novel drugs.
In this study, we tested the impact on survival of disease‐ and patient‐related parameters in a large cohort of elderly AML patients assigned to treatment with HMAs.
1 Division of Hematology and Cellular Therapies Unit Carlo Melzi, Dept. of Morphological and Medical Research, University of Udine
2 II Hematology Division, San Martino Hospital, Genoa
3 Statistics ...Institute, Dept. of Morphological and Medical Research, University of Udine
4 Hematology Division, La Sapienza University, Rome
5 Hematology Department, Pescara Hospital, Oncohematology Unit
6 La Maddalena Hospital, Palermo
7 Internal Medicine and Hematology Division, S. Gerardo de Tintori Hospital, Monza
8 Division of Hematology, Pesaro Hospital
9 Division of Hematology, Reggio Calabria Hospital
10 Hematology Division, Azienda Ospedaliera Careggi, University of Florence, Italy
Correspondence: Francesca Patriarca, MD, Division of Hematology and Cellular Therapies Unit Carlo Melzi, Azienda Ospedaliera-Universitaria p.zale S. Maria della Misericordia 1, 33100 Udine, Italy. E-mail: patriarca.francesca{at}aoud.sanita.fvg.it
Background: Allogeneic stem cell transplantation is a potentially curative treatment for myelofibrosis, although its use is limited by a high rate of transplant-related mortality. In this study, we evaluated the outcome of patients with myelofibrosis who underwent allogeneic stem cell transplantation, and the impact of prognostic factors.
Design and Methods: One hundred patients were transplanted in 26 Italian centers between 1986 and 2006. We analyzed the influence of the patients characteristics and the clnical features of their disease before stem cell transplantation and of transplant procedures on transplant-related mortality, overall survival, and relapse-free survival by means of univariate and multivariate analyses.
Results: The median age of the patients at the time of stem cell transplantation was 49 years (range, 21–68) and 90% of them had an intermediate or high Dupriez score. Forty-eight percent received a myeloablative conditioning regimen and 78% received stem cells from matched sibling donors. The cumulative incidence of engraftment at day 90 after transplant was 87% (95% CI, 0.87–0.97). The cumulative 1-year and 3-year incidences of transplant-related mortality were 35% and 43%, respectively. The estimated 3-year overall and relapse-free survival rates after stem cell transplantation were 42% and 35%, respectively. In multivariate analysis, negative predictors of transplant-related mortality were year of stem cell transplantation before 1995, unrelated donor, and a long interval between diagnosis and transplantation. There was a trend towards longer overall and relapse-free survival in patients receiving peripheral blood stem cells rather than bone marrow as the source of their graft ( p =0.070 and p =0.077, respectively). The intensity of the conditioning regimen (myeloablative versus reduced intensity regimens) did not significantly influence the outcome.
Conclusions: We conclude that the outcome of myelofibrosis patients who underwent allogeneic stem cell transplantation significantly improved after 1996 due to the reduction in transplant-related mortality. We observed that a reduction in transplant-related mortality was associated with the choice of a matched sibling donor, whereas longer overall survival was associated with the use of peripheral blood as the source of stem cells.
Key words: primary myelofibrosis, allogeneic stem cell transplantation, prognostic factors, reduced-intensity regimens.
Related Article
Allogeneic hematopoietic stem cell transplantation for myelofibrosis
Damiano Rondelli
Haematologica 2008 93: 1449-1450.
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Despite recent advances, allografting remains the only potential cure for myeloma. From July 1999 to June 2005, 100 newly diagnosed patients younger than 65 years were enrolled in a prospective ...multicenter study. First-line treatment included vincristin, adriamycin, and dexamethasone (VAD)–based induction chemotherapy, a cytoreductive autograft (melphalan 200 mg/m2) followed by a single dose of nonmyeloablative total body irradiation and allografting from an human leukocyte antigen (HLA)–identical sibling. Primary end points were the overall survival (OS) and event-free survival (EFS) from diagnosis. After a median follow-up of 5 years, OS was not reached, and EFS was 37 months. Incidences of acute and chronic graft-versus-host disease (GVHD) were 38% and 50%, respectively. Complete remission (CR) was achieved in 53% of patients. Profound cytoreduction (CR or very good partial remission) before allografting was associated with achievement of posttransplantation CR (hazard ratio HR 2.20, P = .03) and longer EFS (HR 0.33, P < .01). Conversely, development of chronic GVHD was not correlated with CR or response duration. This tandem transplantation approach allows prolonged survival and long-term disease control in patients with reduced tumor burden at the time of allografting. We are currently investigating the role of “new drugs” in intensifying pretransplantation cytoreduction and posttransplantation graft-versus-myeloma effects to further improve clinical outcomes. (http://ClinicalTrials.gov; NCT-00702247.)
BACKGROUND: In the past two decades peripheral blood stem cells (PBSCs) have increasingly replaced marrow as stem cells source for allogeneic transplantation. The PBSC donation initially applied only ...to related donors; later, due to the safety of the procedure, it was extended to unrelated donors.
STUDY DESIGN AND METHODS: We have retrospectively collected data regarding mobilization, collection, and short‐ and long‐term follow‐up of 190 consecutive donors, 174 related and 16 unrelated. All donors followed a standard protocol for mobilization and underwent at least one PBSC collection. Follow‐up in related donors was performed every 4 months in the first year and then annually, with no time limits, while unrelated donors were monitored for 10 years.
RESULTS: All 190 donors completed the established mobilization protocol. The mobilizing capacity was significantly greater in males and in donors less than 60 years old. No case of major toxicity by granulocyte–colony‐stimulating factor was found, nor thromboembolic events. The total dose of CD34+/recipient (median 5.8 × 106/kg recipient/body weight) was statistically correlated with age, CD34+ before and after mobilization, and collection efficiency. Compliance to follow‐up was 66%, with a significant difference between related and unrelated (63% vs. 100%, p = 0.03). During follow‐up no significant abnormalities in hematologic variables or hematologic malignancies were reported.
CONCLUSION: Our study allowed us to define the PBSC donation as “a safe procedure for the donors,” with short‐ and long‐term effects limited to a small percentage of donors and “effective for the recipient,” due to the dose of collected CD34+, adequate for transplantation in almost all recipients.
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