JAK2 Inhibitors RUXOLITINIB in Patients With Myelofibrosis

JAK2 inhibitor RUXOLITINIB before allogeneic hematopoietic stem cell transplantation (HSCT) in patients with primary or secondary myelofibrosis

Inclusion criteria

• Age between 18 and 69 years
• No comorbidity contraindicating the transplantation :

• Severe respiratory failure defined as dyspnea grade III or more
• Severe cardiac failure defined as EF < or = 30%
• Severe renal failure defined as creatinine clearance < 30 ml/min or dialysis
• Dementia or non-ability to give informed consent for the protocol
• Major alteration of performance status defined as ECOG > 2
• Severe liver disease defined as a cirrhosis or bilirubin > 2 x ULN, or AST/ALT > 5 x ULN
• Primary or secondary myelofibrosis diagnosed according to WHO definition (Tefferi, et al 2007)
• Palpable splenomegaly or splenomegaly measured by any imagery (maximum size> 15 cm by ultrasound scan, Magnetic Resonance Imaging or computer tomography)
• Disease if intermediate or high risk according to published criteria and summarized as follows:

At least one criterion among the following:

• Haemoglobin < 100 gr/L (unrelated to medication toxicity)
• Leucocytes < 4 G/L (unrelated to medication toxicity) or > 25 G/L
• Poor prognosis cytogenetics : complex karyotype, abnormalities of chromosomes 5, 7 or 17 , +8, 12p-, inv(3), 11q23

Two criteria among the following criteria :

• General symptoms (weight lost > 10% in less than 6 months, night swears, specific fever > 37.5°C)
• Peripheral blastosis > 1% observed at least twice
• Thrombocytopenia < 100 G/L (unrelated to treatment toxicity)

Exclusion criteria

• Myelofibrosis transformed into acute leukaemia with 20% blasts of more in blood or bone marrow
• Previous treatment with JAK2 inhibitor
• Thrombopenia < 50 G/L
• Comorbidities contraindicating the transplantation
• Comorbidity score Sorror > 3
• Pregnant or lactating women