Objective: Myelofibrosis with myeloid metaplasia (MMM) is a clonal myeloproliferative disorder of later life not generally considered for allogeneic haematopoietic cell transplantation (alloHCT) until recently. The natural course of the disease varies greatly but is eventually fatal in all. We present the results of 35 consecutive transplants for MMM during the last six years in our institution. - Material and Methods: 25 males and 10 females with primary (n=29) and secondary MMM (n=6) were grafted with unmanipulated bone marrow (n=21) or peripheral stem cells (n=14) from a related (n=10) or unrelated (n=25) donor. Median (md) age was 51 (33-64) years. Ten patients (pts) had low, 15 intermediate and 10 high risk disease (Dupriez score 0, 1, 2). 28 pts had a modified Charlson comorbidity index (CCI, Diaconescu et al, Blood 104, 2004: 1550) of 0 to 2, seven one of 3 to 6. Karyotyping was successful in 29 pts and abnormal in 12. All but four pts received intermediate intensity conditioning (TBI(8Gy)/Flud/Cy n = 21 or Bu(10)/Flud n = 10). In all unrelated and two related transplants rabbit ATG was added before grafting. - Results: All pts engrafted at a md of 22 (11-41) days. 6 pts lost complete chimerism during follow up with proven relapse at a md of 401 days in four. At a md follow up of 23 (4-79) months probability of overall (OS) vs eventfree survival (EFS) was 74% vs 50% for the whole cohort. A trend towards better survival was seen in recipients of related compared to unrelated transplants (100 vs 64 %, p=0.06) and in those with less advanced disease (90 vs 68 % in Dupriez 0 vs 1+2, p=0.26). However the only significant predictor for OS by log rank test was the pretransplant CCI: 85 vs 34 % in pts with CCI 0 to 2 vs 3 to 6 (p=0.01). Probability of EFS at day 480 was significantly less in pts with abnormal karyoptype compared to those with no detectable anomalies (17 vs 61%, p=0.01). Five pts with decreasing chimerism received immunotherapy (3 DLI, 2 PBSC) with return to complete chimerism in three and postDLI aplasia in one.- Conclusions: Our results support the use of related and unrelated alloHCT as a curative treatment option in MMM. Outcome is better in pts without disease associated and disease independent comorbidity. For pts with abnormal karyotype there is a considerable risk of relapse/reversal post transplant. Especially in risk pts chimerism therefore should be monitored closely as disease recurrence may respond to immunotherapy.

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, Blood 93, 1999: 2831; Deeg et al, Blood 102, 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.