Cytopenias

Sharing on behalf of Dr. Kim Nichols,

Dear NICER colleagues, In collaboration with the North American Consortium for Histiocytosis (NACHO), Melissa Hines and I are running a clinical trial investigating the efficacy and tolerability of a response-adapted ruxolitinib-containing regimen for children with newly diagnosed or relapsed/refractory HLH. The protocol is now open at 10 participating sites, including:

• St. Jude Children’s Research Hospital – Memphis, TN

• Children’s Hospital of Philadelphia – Philadelphia, PA

Hi Rohith -

Sounds like a tough case. My understanding from previous conversations was that Pharming is planning a pediatric leniolisib trial for the US "early" this year. I'm not sure how far along they are (or aren't) in the execution of the study, but it may be worth reaching out to see what information they have. Joe Harper (j.harper@pharming.com) has been a point of contact for NICER in the past and may have information related to the anticipated trial/compassionate use options.

From my end, sirolimus seems reasonable as a starting point. Koneti Rao (korao@niaid.nih.gov) would likely have additional insights on how well patients similar to yours have done with sirolimus vs HSCT.

Hi everyone!

In our hematology department, we have a 3yo male with a recent history of multiple infections, anemia, thrombocytopenia, splenomegaly, lymphadenopathy, and CD4 lymphopenia. He also has a history of CMV positivity and elevated IgG levels. PID NGS panel found a pathogenic GOF mutation in the PIK3CD gene, c.3061G>A, p.Glu1021Lys. This is a mutation that has been reported in several individuals with PI3Kδ syndrome.

In view of cytopenias and organomegaly, we intend to start treatment shortly. Last year during one of our monthly conferences we discuss the use of Idelalisib as an alternative to Sirolimus. The clinical trial does not appear to include children <12 years of age. We are currently thinking of initiating sirolimus but wanted to see if there are any other alternatives.

One of my colleagues have sent it to the CIS listserv so I will update y'all if we get any additional ideas.

Rohith