Spontaneous Remission Of Granulocyte Colony-stimulating Factor–associated Leukemia In A Child With Severe Congenital Neutropenia
Jeha, S., Chan, K. W., Aprikyan, A. G., Hoots, W. K., Culberight, S., Zietz, H., Dale, D. C., & Albitar, M. (2000). spontaneous remission of granulocyte colony-stimulating factor-associated leukemia in a child with severe congenital neutropenia. Blood, 96(10), 3647–3649. https://doi.org/10.1182/blood.v96.10.3647
Abstract
Leukemia is observed with increased frequency in patients with severe congenital neutropenia (SCN). In the past decade, recombinant human granulocyte colony-stimulating factor (rh G-CSF) has prolonged the survival of patients with SCN increasingly reported to have leukemias. In this communication acute myelogenous leukemia (AML) associated with a mutation of the G-CSF receptor (G-CSF-R) developed in a patient with SCN maintained on long-term G-CSF therapy. The blast count in the blood and bone marrow fell to undetectable levels twice on withholding G-CSF and without chemotherapy administration, but the mutant G-CSF-R was detectable during this period. The patient subsequently underwent successful allogeneic bone marrow transplantation. After transplantation, the patient's neutrophil elastase (ELA-2) mutation and G-CSF-R mutation became undetectable by polymerase chain reaction. This report provides novel insights on leukemia developing in congenital neutropenia.
Case Details
Disease Location
Bone marrowithblood
Personal Characteristics
12 -year-old male received a diagnosis of severe neutropenia at the age of 3 months during the first 3 years of life, he was admitted more than 30 times for life-threatening infections at 3 years old, g-csf treatment was begun which responded excelletnly to allowing him to lead anormal life for 9 years
Clinical Characteristics
On june 8, 1999, severe left otitis associated with extensive cellulitis developed on the left side of the face cbc showed hgb 11, platelets 153,000; wbc 11,800; and 32% myeloperoxidase-positive blasts marrow aspirate confirmed acute myeloid leukemia diagnosis with 73% blasts, myeloperoxidase positive, CD34 97.5%, CD13 92.6%, and CD33 31.4% cytogenetics assay showed a pseudodiploid clone 46,xy, add (18)(q23) in 18 metaphases and a diploid male karyotype 46,xy in 2 metaphases g-csf was discontinued and the patient begun treatment with IV antibiotics when remission was documented, patient restarted g-csf to maintain his neutrophil count marrow aspirate taken 7 weeks after g-csf was restarted showed 40% myeloperoxidase-positive blasts with reappearance of the old 18q+ clone and a new clone with trisomy 21 g-csf was interrupatiented and again
Remission Characteristics
After 5 days on antibiotics, the infection had improved and the wbc count gradually decreased, chemo and g-csf was withheld, but prophylactic antibiotics were maintained after 4 weeks without g-csf, repeat marrow aspirate showed complete morphological and cytogenetic remission that lasted for 11 weeks. When g-csf was interrupatiented again, the patient achieved a second remission in 14 days after 6 weeks in complete remission, he underwent match, unrelated marrow transplantation 6 months after the transplant, the leukemia remains in remission
Treatment & Mechanisms
Proposed Remission Mechanisms
No major mechanism proposed but remission seemed associated to when g-csf was withdrawn
Clinical Treatment
G-csf IV antibiotics/prophylactic marrow transplant
Non-Clinical Treatment
None reported