Neutropenia during Hematopoietic Stem Cell Mobilization with G-CSF

A 36-year-old female was referred to our hematology department for HSC donation by leukapheresis of peripheral blood after mobilization. On the first day she was informed of adverse events of HSC harvesting and then signed an agreement. She denied of having any severe or chronic disorders before. No abnormal signs are found in physical and laboratory examination. Laboratory data showed normal blood routine test (WBC 3.77X10E9/L, LYM 0.61X10E9/L NEU 1.68X10E9/L, HGB 128 g/L and PLT 174X10E9/L), negative test for HBV, HCV, HIV, Toxoplasmosis and Treponemapallidum. Quantitation of both cytomegalovirus and Epstein-Barr virus DNA were <500 copies/mL. She was administrated with 300u G-CSF (FILGRASTIM, Kirin-Amgen) by subcutaneous injection at 16:00, then once a day in the morning. Norethisterone tablets were given 5000ug TID daily to delay the coming menstruation, which had been used routinely for many years safely for this purpose in our hospital, altogether total dose of Norethisterone tablets 30000ug in 48 hours.

On the third day of G-CSF administration, blood routine test amazingly showed a sharply declined Neutrophilic Granulocyte count (NEU) of 0.54X10E9/L, reduced lymphocyte count (LYM) of 0.77X10E9/L and normal Monocyte count (MON) of 0.56X10E9/L, normal Hematoglobin (HGB) of 127 g/L and normal platelet count (PLT) of 150X10E9/L. She was diagnosed with Neutropenia. During re-inquiring for her medical history, she admitted that she was diagnosed with Adult Onset Still’s Disease (AOSD) when she was 18 y.o. which relapsed at 24. She was given aspirin and achieved remission of the symptoms. She denied any history of allergy. The donor did not complain about any symptoms and her body temperature was 36°C. Norethisterone tablets administration was stopped. At 16:00 of the third day, additional 300u G-CSF was administrated for Neutropenia. At 17:21, blood sample showed NEU 0.50X10E9/L, Agranulocytosis indicated, and an evaluated MON of 0.77X10E9/L; normal coagulation function, evaluated ESR of 31mm/h, slightly reduced complement 3 of 0.87 g/L (normal: 0.9 to 1.8 g/L) and evaluated total complement of 50.1 U/mL (normal: 23.0 to 46.0 U/mL) was showed; on the next day afternoon, strong positive (3+) test for anti-RO52 and negative test for ANA, anti-DS-DNA, anti-Jo-1, ANCA, anti-SS-A or anti-SS-B in autoimmune antibody was reported. Abdominal ultrasonography reported normal size of her liver and spleen.

On the fourth day, 300u G-CSF was administrated the fifth time at 10:00. After that, blood sample was collected and showed WBC of 2.22X10E9/L, LYM of 0.86X10E9/L, NEU of 0.52X10E9/L, MON of 0.83X10E9/L, HGB of 133 g/L and PLT of 153X10E9/L. Bone marrow aspiration showed myeloid hyperplasia (-), hypoplasia and abnormal maturation in granule cell, left shift with toxic granulation. CD34+ cell ratio reported 1.4% (marrow) and 0.2% (peripheral blood), which revealed HSC mobilization was failed.

On the fifth day, G-CSF was not administrated. Blood sample collected at 12:00, 26 hours after the last G-CSF administration, revealed WBC of 3.94X10E9/L, LYMX1.31 10E9/L, NEU 1.08 X10E9/L, MON 1.48X10E9/L, HGB of 125 g/L and PLT of 151X10E9/L. The donor seemed recovering from Neutropenia.

At 12:00 on the sixth day, bone marrow was collected for transplantation. Blood routine test showed WBC of 4.03X10E9/L, LYM 0.84X10E9/L, NEU 2.38X10E9/L, MON 0.78X10E9/L, HGB of 94 g/L and PLT of 129X10E9/L.

We described a HSC donor with AOSD history who developed Neutropenia subsequent to subcutaneous injection of G-SCF and recovered in 2 days after the last administration. Neutropenia caused by Norethisterone tablets was not common and we didn’t find any report that combined medication of norethisterone tablets and G-CSF would cause neutropenia. The donor didn’t complain any symptoms and we couldn’t find any typical signs in the process, which indicated Neutropenia might be unrelated with infection or allergy.

It may be the first case of this situation, we have not yet confirmed the cause of her Neutropenia. We preserved samples of blood and marrow aspiration under the donor’s consent and we will have further research and follow-up with this case.