Allogeneic hematopoietic cell transplantation in myelofibrosis with myeloid metaplasia.
Myelofibrosis with myeloid metaplasia is a clonal disorder resulting from proliferation of aberrant hematopoietic progenitors. It can occur either de novo or secondary to an antecedent chronic myeloid disorder such as essential thrombocythemia or polycythemia vera. The only curative option is allogeneic hematopoietic cell trans-plantation, which can result in durable donor engraftment and regression of myelofibrosis in approximately 50% of eligible patients. Unfortunately the median age at presentation is 65 years and many patients have serious comorbidities, so the vast majority of patients are excluded from such an approach. Reduced-intensity conditioning regimens have been shown to result in successful engraftment and resolution of myelofibrosis with less toxicity, although follow-up remains relatively short. Complications such as graft-versus-host disease remain the major barrier to greater success. At present this modality is generally restricted to younger patients with intermediate-to high-risk disease. We provide a current algorithm for incorporating allogeneic transplantation into the management of patients with myelofibrosis. We are hopeful that recent advances in allogeneic transplantation, combined with progress in understanding the molecular pathobiology of chronic myeloproliferative disorders, will lead in the near future to a further refinement of prognostic determinants, new molecular targets to exploit, and therefore a dynamic evolution of the indications for allogeneic transplantation.
Hogan
William J
WJ
Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. hogan.william@mayo.edu
Litzow
Mark R
MR
Tefferi
Ayalew
A
D000328:Adult; D000368:Aged; D002986:Clinical Trials as Topic; D015897:Comorbidity; D015507:Drugs, Investigational / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense; D019653:Myeloablative Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018579:Patient Selection; D017354:Point Mutation; D055728:Primary Myelofibrosis / Q000188:drug therapy / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics / Q000601:surgery*; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D012306:Risk; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D014184:Transplantation, Homologous / Q000009:adverse effects; D055815:Young Adult
D015507:Drugs, Investigational; D019653:Myeloablative Agonists; D047428:Protein Kinase Inhibitors; C507924:JAK2 protein, human; D053614:Janus Kinase 2