Chronic Neutrophilic Leukemia - Stem Cell Transplantation in a Very Young Patient

Background: Chronic neutrophilic leukemia (CNL) is a rare BCR/ABL negative myeloproliferative neoplasm (MPN) characterized by sustained, predominantly mature neutrophil proliferation, bone marrow granulocytic hyperplasia, and hepatosplenomegaly. CSF3R mutation is a central diagnostic criterion. Most patients are over the age of 60 and the median survival is estimated at 2 years. No effective standard therapy has been established yet.

Case-report: In March 2019 a 29 y/o male presented with cough, arthralgias, and hepatosplenomegaly. His initial WBC was 47.000/µl with 80% neutrophils, few neutrophil progenitors, no monocytosis. Bone marrow was consistent with a myeloproliferative syndrome, particularly CML, however BCR/ABL was negative. Flow cytometry suggested a myelodysplastic syndrome (MDS Score ↑) und with the preliminary diagnosis of mixed MPN/MDS he received one course of azacytidine without response. After this course we received the results of molecular genetic analysis which showed CSF3R c.1853C>T (also pos. for DNMT3A, IDH2, neg. for JAK2, CALR, PDGFRα/β, FGFR1). WBC increased further to 77.000/µl and we initiated hydroxyurea and - after insurance granted coverage - switched to ruxolitinib (initially 10 mg BID, then 15 mg BID). His hepatosplenomegaly responded and WBC came down slowly. In August he started to lose response, WBC rose again, and he needed blood transfusions.

Because of his young age we had planned stem cell transplantation from the very beginning. The main purpose of ruxolitinib had been to reduce pre-transplant leukemic burden. Bone marrow from March 2019 showed 2% CD34+ cells, in Sept. 4%, Jan 2020 20-25%, consistent with transformation to AML. There was no family donor. In March 2020 he underwent allogeneic stem cell transplantation from a matched female unrelated donor (MUD allo-SCT 10/10 match) which he tolerated well. Conditioning was busulfan based.

His further clinical course was complicated starting d+40 after SZT with °IV gastrointestinal GvHD (no CMV or other infectious agent identified). Immunosuppression had to be escalated using steroids (1 mg/kg BW BID) + ruxolitinib + photopheresis. Eventually AML recurred and the patient deceased on d +81 due to multi organ failure induced by refractory GvHD and AML recurrence.

Conclusion: As most described cases of CNL occur in elderly patients reports on stem cell transplantation are rare. Here we present the course of a 29 y/o male who had only a short response to ruxolitinib and hydroxyurea. Both agents did not alter the bone marrow leukemic burden, therefore he proceeded to alloSCT. He did not achieve a sustained remission. We decided to present this case despite the unfortunate outcome because - to our knowledge - there has been no prior report on alloSCT in such a young patient with CNL.