Neutropenia a frequent occurrence in ADA-SCID

Neutropenia a frequent occurrence in ADA-SCID

Published Date: 15/10/18

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medwireNews: Neutropenia could be a presenting feature of adenosine deaminase deficient-severe combined immunodeficiency (ADA-SCID), say investigators after detecting it in more than half of the patients in their chart review.

Therefore, they recommend that ADA deficiency “be considered in infants presenting with SCID and neutropenia.”

The team writes that “there are no specific predisposing factors that predict the development of neutropenia; hence, complete blood cell count should be monitored closely among all ADA-deficient patients.”

As reported in The Journal of Allergy and Clinical Immunology, neutropenia was detected in 13 (65%) of the 20 patients diagnosed with ADA-SCID at a Canadian hospital between 1985 and 2015, with the neutropenia diagnosed in just three patients before the age of 3 weeks and in the rest when they were older, following initial normal counts.

On the whole, the neutropenia tended to be mild, but four patients had an absolute neutrophil count (ANC) of 0.5×109/L, which the study authors say “is considered severe.”

Eleven patients achieved a normal ANC after experiencing neutropenia for 6–456 days, with spontaneous resolution occurring in just four patients. In the remaining seven patients, the neutropenia resolved only after they received enzyme replacement therapy or haematopoietic stem cell transplantation (HSCT) for ADA-SCID.

One patient died at 213 days while still neutropenic and another had ongoing neutropenia at the most recent assessment, at 1450 days.

Researcher Eyal Grunebaum (The Hospital for Sick Children, Toronto, Ontario, Canada) and colleagues explain that treatment with antimicrobials, such as trimethoprim–sulfamethoxazole (TMP–SMZ), has previously been implicated in the development of neutropenia. However, eight of the neutropenic patients in their cohort were not receiving TMP–SMZ, whereas the seven children who did not develop neutropenia were.

Furthermore, they point out that among the five TMP–SMZ-treated patients who developed neutropenia, it “appeared to be transient and mild, questioning the practice of discontinuation of this important treatment.”

The investigators were unable to determine “[w]hether the presence of neutropenia in the patients reported here could be a harbinger of impending myelodysplasia” as the condition generally resolved, but they highlight that no patient developed a myeloid malignancy over the study period.

Noting that neutropenia “often emerged before the effects of potential confounding factors including infections or treatments such as HSCT or [gene therapy]”, Grunebaum et al conclude that their study “confirms that the lack of ADA directly predisposes to myeloid abnormalities.”

They continue: “Future studies will be required to further clarify the mechanism(s) leading to the myeloid abnormalities in ADA deficiency.”

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