Abstract
Introduction: MMM is a clonal myeloproliferative disorder of later life with a wide range of life expectancy from months to many years. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment option, however associated with considerable morbidity and mortality. We analyzed the results of HSCT in 15 consecutive patients (pts) with MMM referred to our institution during the last four years in order to determine the best time point for transplantation.
Patients and Methods: Ten males and five females with primary (n = 13) and secondary MMM following myeloproliferative syndrome (n = 2) were grafted with unmanipulated bone marrow (n = 10) or peripheral stem cells (n = 5) from a related (n = 6) or unrelated (n = 9) donor. Median (md) age was 49 (36 – 64) years, md time from diagnosis to transplant 27 (6 – 132) months. Five pts had low, eight intermediate and two high risk disease (Dupriez score 0, 1, 2). All intermediate risk pts were categorized Dupriez 1 because of hemoglobin levels (Hb) < 10 g/dl. In low risk pts indication for transplant were severe constitutional symptoms. Mean risk score was 0.4 (0–1) in related and 1.1 (0–2) in unrelated transplants. 8 pts were transfusion dependent and two had portal hypertension. Eleven pts received a conditioning of intermediate intensity containing TBI(8Gy)/Flud/Cy (n = 10) or Bu(12)/Flud (n = 1). Four pts had standard TBI/Cy or Bu/Cy (n = 2 each). GvHD prophylaxis consisted of CsA and short course MTX. In all unrelated and two related transplants rabbit ATG (Genzyme n = 6, Fresenius n = 5) was added before grafting.
Results: All pts engrafted at a md of 23 (11 – 28) days. Four pts developed extended cGvHD. Four pts died at a md of 266 (177–407) days: One from liver cirrhosis, one from cerebral aspergillosis and two from infections associated with cGvHD. At a md follow up of 21 (4 – 53) months probability of disease free survival (DFS) is 66% for the whole cohort and 100% vs 45% for pts with a related versus an unrelated donor. Results of MUD transplants are confounded with the higher risk score of pts grafted from an unrelated donor, as DFS according to disease risk was 100% for score 0 and 52% for score 1 and 2. Need for red blood cell transfusions before transplant was an even better predictor of DFS with 100% in untransfused and 36% in transfusion dependent pts. A log rank test was performed for the following variables: Conditioning intensity, donor type (MUD vs MRD), stem cell source, Dupriez score and need for blood transfusions: Only transfusion dependence proved to be significant (p = 0.03).
Conclusions: Although the number of pts is small our results support the use of related and unrelated allogeneic SCT as a curative treatment option in MMM. Hb below 10 g/dl has been reported to be a predictor of adverse outcome after HSCT (Guardiola et al, Blood93, 1999: 2831; Deeg et al, Blood102, 2003: 3912). In our hands however, red cell transfusion dependence is the relevant cut off point for survival as pts with risk score 1 without need for transfusions had the same DFS as pts with risk score 0. Transfusion dependence may be a marker of disease progression and of increased toxicity at a time. AlloHSCT therefore should be performed earlier during the natural course of the disease, ie before transfusion dependence occurs, when DFS is excellent.
Managing thalassemia in the developing world: an evidence-based approach for prevention, transfusion independency, and curative treatment with hematopoietic stem cell transplantation
