Extended use of granulocyte colony-stimulating factor (GCSF) for severe chronic neutropenia (SCN), the preferred treatment choice for the illness for decades, tends to be effective and safe, with worse outcomes seen in congenital cases, according to long-term findings from the Severe Chronic Neutropenia International Registry (SCNIR) recently reported in Blood Advances.
“Long-term SCNIR follow-up indicates that the risk for severe hematological outcomes – e.g., myeloid malignancies – resides almost exclusively in patients with congenital neutropenia,” according to the researchers, led by David Dale, MD, professor of medicine at the University of Washington. “In most cases, these develop several years after the start of GCSF.”
The SCNIR was created in 1994 after approval of GCSF for SCN to log safety observations. Since then, 1,752 patients meeting the criteria for the registry have contributed data, with an average follow-up of 9.3 years. Among participants, 189 patients have 15 to 20 years of follow-up, and 82 patients have more than 25 years of follow-up.
Two of the main goals of GCSF treatment, which triggers the growth of neutrophils, is to prevent serious infections and the development of myeloid and lymphoid cancers. The present study findings suggest the treatment does this quite well, with just 36 deaths from infection and 77 cases of acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS).
Researchers analyzed outcomes for those with congenital SCN, cyclic SCN characterized by recurring episodes of low neutrophil counts, and autoimmune or idiopathic SCN. Of the 670 patients in the registry with congenital SCN, 76 (11.3%) developed AML or MDS. Just one of the 266 with the cyclic form of SCN developed AML or MDS, and none of the 816 with the autoimmune or idiopathic form did.
Development of lymphoproliferative disease was also uncommon. There were just three cases among the 670 patients with congenital SCN, none among the 266 patients with cyclic SCN, and 12 among the 816 patients with autoimmune or idiopathic SCN.
“When we began SCNIR, it was unknown if this potent growth factor would alter growth or predispose malignancies,” the researchers noted. “We have not observed either.”
Patients with congenital SCN fared worse than the other groups when it came to deaths from infection, with 21 deaths from infection (3.1%) among these patients, compared to 2.6% among the patients with cyclic SN and less than 1% for the patients with autoimmune or idiopathic disease.
Researchers also pulled outcomes for hematopoietic cell transplant (HCT) for patients who developed AML or MDS due to SCN, which became a more standard treatment in 2000. They found that outcomes improved over time, with five of 19 patients (26%) surviving before 2000 and 18 of 45 patients (45%) surviving since 2000.
Researchers found that GCSF increased neutrophil counts for nearly all patients, and while patients experienced a pattern of infections and fever before treatment, this dissipated after treatment.
“We believe this is the basis for patient acceptance of daily, alternate-day, or thrice weekly GCSF treatment, despite injection discomfort and some bone pain,” they noted. “There was excellent adherence observed during a long period when GCSF vials were returned and counted. Hospital records indicate that stays for infections decreased – before versus after GCSF – and death from infections decreased.”
The researchers pointed out the limitations of their study, including the incomplete definition of the immunological status of patients with autoimmune or idiopathic neutropenia, lack of genetic analyses for all patients, and lack of standardization of the timing and reading of bone marrow examinations.
The researchers encouraged more support for genetic analyses so that outcomes and treatments for genetic subtypes can be better understood.
“Nevertheless,” the researchers noted, “the SCNIR has demonstrated the value of a registry to collect and longitudinally analyze data to describe clinical outcomes for patients with rare diseases causing [SCN].”
Any conflicts of interest declared by the authors can be found in the original article.
Dale DC, Bolyard AA, Shannon JA, et al. Outcomes for patients with severe chronic neutropenia treated with granulocyte colony-stimulating factor. Blood Adv. 2022;6(13):3861-3869.