5.2.4Management

•Treatment strategy: curative treatment, maintenance of chronic phase, palliative

•Drugs: imatinib mesylate (see below), interferon-alpha (see below), cytotoxic agents (busulfan,hydroxyurea, ara-C; rarely used). Allogeneic hematopoietic stem- cell transplantation

–Tyrosine kinase inhibitors, such as imatinib mesylate, have replaced all other initial treatment approaches for patients with newly diagnosed CML. Success particularly in patients in the chronic phase. However, many unanswered ques- tions remain (pediatric aspects, timing, dosage, combination with other drugs, role in stem cell transplantation and in relapse). Since 1998 more than 15,000 patients treated. A complete remission of 68% observed in adults with newly diagnosed CML, i.e., chronic phase, in contrast to interferon-alpha and ara-C, in 7% of patients. The pretreatment of patients with tyrosine kinase inhibitors prior to transplant does not adversely affect outcomes and there is some evi- dence that improved outcomes are observed. Because of the equivalent or slightly better outcomes of patients treated with TK inhibitors compared to transplantation, the decision to proceed with transplantation has become much more complex, especially in young adults. While transplantation remains the only definitively proven cure of CML, long-term outcomes in adults with CML treated with TK inhibitors continues to be encouraging. Key elements that influence prognosis are the initial cytogenetic and molecular responses to TK inhibitors and negative minimal residual disease during treatment

•TK inhibitors, such as imatinib, also have activity in accelerated phase and in blast crisis but remissions are usually short

5.3Polycythemia Vera

5.3.1Diagnosis

•Increased red cell mass

•Arterial oxygen saturation, 92% in association with splenomegaly or two of the following factors:

–Thrombocytosis (more than 600 × 109 thrombocytes/l)

–Leukocytosis (more than 12 × 109 leukocytes/l)

–Increased leukocyte alkaline phosphatase or increased vitamin B12-binding capacity

•Additional criteria: low erythropoietin concentration, spontaneous synthesis

•Somatic JAK2 V617F mutation may be present; a high mutant to normal allele ratio provides a more accurate diagnosis

•Extremely rare in childhood

•Young age does not protect from complications of polycythemia vera (PV). Complications are often present at the time of diagnosis

•Autosomal recessive and dominant forms have been reported