Severe congenital neutropenia (SCN) is a constellation of syndromes consisting of arrested myeloid development resulting in neutropenia. The mainstay of treatment is G-CSF. It is not, however, a curative treatment. Approximately 90% of patients respond to GCSF administration with a subsequent decrease in sepsis-related mortality to almost 1% per year during the first decade of life, with a cumulative incidence of 21% of progression to acute leukemia following 10 years of GCSF. Recently updated North American registry data suggest a relative plateau in the hematologic malignancy risk after 10–15 years. It remains controversial if prolonged GCSF therapy predisposes to malignant transformation.
Allogeneic sem cell transplantation is curative. Zeidler et al. reported 11 SCN patients without malignancy who received HSCT; 8 received sibling-matched transplants (5 BMT, 1 cord, 1 BMT and cord, 1 PBSC) and 10 received myeloablative conditioning with busulfan/cyclophosphamide ± ATG, thiotepa, or melphalan. All patients receiving myeloablative conditioning engrafted regardless of source although 40% of tested patients had graft chimerism (30%–84% donor) at 6–12 months post-transplant. Acute GVHD grade II–IV was present in 2 of the unrelated BMT recipients. Overall survival of the 10 patients receiving myeloablative regimens was 80% at median follow-up of 10 months. The French SCN registry reported HSCT outcomes on 5 SCN patients without malignant transformation. Donors included unrelated cords (2) and unrelated bone marrows (2), and related bone marrow (1). All received myeloablative regimens with 80% engraftment and 40% mortality due to infection at one year post-transplant. In contrast, 18 Japanese patients with SCN without malignant transformation underwent transplantation from sibling-matched (9) or matched-unrelated donors (9) following myeloablative conditioning in 12 cases and non-myeloablative in the remaining 6 patients. Although four patients encountered primary graft failure (including two sibling matched donor transplants) and received a second transplant, 16 of the 18 patients are considered disease-free with a median follow-up of 6 years.
It appears form reproted series and cases that it is far better to transplant before AML or MDS develop.
Transplantation is indicated for patients unresponsive to GCSF and should be strongly considered for mild responders to high doses of GCSF given this group’s risk of malignancy and the disparity between transplant survival prior to malignant transformation compared to afterwards.
Sung W. Choi, John Levine Indications for hematopoietic cell transplantation for children with severe congenital neutropenia Pediatric Transplantation Volume 14, Issue 8, pages 937–939, December 2010
Kenji Morimoto et al, Transplantation for Congenital Bone Marrow Failure Syndromes Bone Marrow Research
Volume 2011 (2011), Article ID 849387, 7 pages
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