Chronic myelogenous leukemia (CML) accounts for less than 5% of all childhood leukemia, and in the pediatric age range, occurs most commonly in older adolescents. The cytogenetic abnormality most characteristic of CML is the Philadelphia chromosome (Ph), which represents a translocation of chromosomes 9 and 22 (t(9;22)) resulting in a BCR-ABL fusion protein. CML is characterized by a marked leukocytosis and is often associated with thrombocytosis, sometimes with abnormal platelet function. Bone marrow aspiration or biopsy reveals hypercellularity with relatively normal granulocytic maturation and no significant increase in leukemic blasts. Although reduced leukocyte alkaline phosphatase activity is seen in CML, this is not a specific finding.
CML has three clinical phases: chronic, accelerated, and blast crisis. Chronic phase, which lasts for approximately 3 years if untreated, usually presents with side effects secondary to hyperleukocytosis such as weakness, fever, night sweats, bone pain, respiratory distress, priapism, left upper quadrant pain (splenomegaly), and, rarely, hearing loss and visual disturbances. The accelerated phase is characterized by progressive splenomegaly, thrombocytopenia, and increased percentage of peripheral and bone marrow blasts, along with accumulation of karyotypic abnormalities in addition to the Ph chromosome. Blast crisis is notable for the bone marrow, showing greater than 30% blasts and a clinical picture that is indistinguishable from acute leukemia. Approximately two-thirds of blast crisis is myeloid, and the remainder is lymphoid, usually of B lineage. Patients in blast crisis will die within a few months.
Many types of leukemia produce no obvious symptoms in the early stages. Eventually, symptoms may include any of the following:
Anemia and related symptoms, such as fatigue, pallor, and a general feeling of illness.
A tendency to bruise or bleed easily, including bleeding from the gums or nose, or blood in the stool or urine.
Susceptibility to infections such as sore throat or bronchial pneumonia, which may be accompanied by headache, low-grade fever, mouth sores, or skin rash.
Before the tyrosine kinase inhibitor era, allogeneic hematopoietic stem cell transplantation (HSCT) was the primary treatment for children with CML. Published reports from this period described survival rates of 70% to 80% when an HLA-matched family donor (MFD) was used in the treatment of children in early chronic phase, with lower survival rates when HLA-matched unrelated donors were used.[4,5,6] Relapse rates were low (less than 20%) when transplant was performed in chronic phase.[4,5] The primary cause of death was treatment-related mortality, which was increased with HLA-matched unrelated donors compared with HLA-MFDs in most reports.[4,5] High-resolution DNA matching for HLA alleles appeared to reduce rates of treatment-related mortality leading to improved outcome for HSCT using unrelated donors. Compared with transplantation in chronic phase, transplantation in accelerated phase or blast crisis and in second chronic phase resulted in significantly reduced survival.[4,5,6] The use of T-lymphocyte depletion to avoid graft-versus-host disease resulted in a higher relapse rate and decreased overall survival (OS), supporting the contribution of a graft-versus-leukemia effect to favorable outcome following allogeneic HSCT.