Transient pancytopenia preceding acute lymphoblastic leukemia (pre-ALL)

Area of Science:

• Pediatric Hematology
• Oncology
• Leukemogenesis

Background:

• Pancytopenia followed by spontaneous recovery can precede acute lymphoblastic leukemia (pre-ALL).
• Pre-ALL is distinct from myelodysplastic syndromes, despite both being preleukemic states.
• Childhood ALL cases show pre-ALL in 2% of instances.

Purpose of the Study:

• To characterize the clinical and hematological features of pre-ALL in children.
• To investigate the potential pathogenetic mechanisms underlying pre-ALL.
• To differentiate pre-ALL from myelodysplastic syndromes.

Main Methods:

• Retrospective analysis of eight children diagnosed with pre-ALL.
• Bone marrow morphology and reticulin fibrosis assessment during the pre-ALL phase.
• Cytogenetic analysis of bone marrow cells during pre-ALL and overt leukemia phases.

Main Results:

• Bone marrow was normo- or hypocellular with increased reticulin fibrosis in pre-ALL.
• No cytogenetic abnormalities were detected in the pre-ALL phase.
• Cytogenetic abnormalities developed in four of six children by the time of overt leukemia.

Conclusions:

• Pre-ALL may represent an early paraneoplastic syndrome in leukemic development.
• Inhibitory properties of clonally expanding, cytogenetically normal cells might mediate pre-ALL.
• Findings suggest a multistep pathogenesis for acute lymphoblastic leukemia.