Bone Marrow Transplantation
https://doi.org/10.1038/s41409-020-0812-x
CORRESPONDENCE
Treatment-related mortality following autologous hematopoietic
stem cell transplantation is unaffected by timing of G-CSF
administration
Naveed Ali
1
●
Brenda Cooper
1
●
Benjamin Tomlinson
1
●
Leland Metheny
1
●
Paolo Caimi
1
●
Kirsten Boughan
1
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Molly Gallogly
1
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Folashade Otegbeye
1
●
Ehsan Malek
1
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Hillard Lazarus
1
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Richard Creger
1
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Marcos de Lima
1
Received: 27 July 2019 / Revised: 17 November 2019 / Accepted: 22 January 2020
© Springer Nature Limited 2020
To the Editor:
High-dose chemotherapy followed by autologous hemato-
poietic stem cell transplant (ASCT) is a standard consolida-
tion therapy for multiple myeloma and lymphoma. Prolonged
neutropenia and serious infections can be associated with
significant morbidity and mortality in these patients.
Granulocyte-colony stimulating factors (G-CSFs) have
clinically demonstrated to accelerate neutrophil engraftment
after ASCT by up to 7 days [1–3]. The American Society of
Clinical Oncology (ASCO) recommends starting G-CSF
1–3 days after high-dose chemotherapy and ASCT, and
continuing until the absolute neutrophil count (ANC) is
≥2000–3000 × 10
6
/L [4]. Despite evidence to support the use
of G-CSF to expedite neutrophil recovery, lack of consensus
with respect to optimal timing of G-CSF initiation exists in
the transplant community and varies among different prac-
tices. Recently, there has been a growing body of interest in
late (≥day +5) G-CSF initiation after ASCT primarily for
cost-effectiveness but also because growth factor-responsive
neutrophilic precursors are not yet formed immediately after
stem cell infusion [5]. Studies compared early (day 0 to
day +4) with late (≥day +5) G-CSF initiation after ASCT
with mixed results regarding neutrophil engraftment, platelet
recovery or number of febrile days [6–10]. Furthermore,
individualized or ANC-driven G-CSF administration did not
affect outcome [11, 12]. Lastly, the usefulness of G-CSF in
patients who receive >5 × 10
6
CD34+ cells/kg is also
unclear.
A clinical practice change was adopted at our institution
in November 2016, where all patients undergoing ASCT
initiated G-CSF on day +5 (late G-CSF initiation cohort),
whereas those prior to November 2016 initiated on the day of
transplantation (early G-CSF initiation cohort). The primary
objective of this retrospective study was to compare time to
neutrophil engraftment between these two cohorts. Second-
ary objectives included infectious complications, length of
hospital stay, treatment-related mortality, and G-CSF cost
difference. The study was approved by Institutional Review
Board (IRB). All consecutive patients aged ≥18 years with
plasma cell neoplasm and lymphoma, who underwent ASCT
from January 2015 to June 2018, were evaluated. Patients
received high-dose chemotherapy and peripherally mobilized
stem cells inpatient. Both cohorts received filgrastim (Neu-
pogen, Amgen) at a dose of 5μg/kg/day (rounded off to the
nearest vial strength; 300 μg or 480 μg). Patients weighing >
100 kg received filgrastim at a dose of 600 μg/day. Filgrastim
was continued until ANC was ≥ 1000 × 10
6
/L for at least 24
hours. Supportive measures including anti-infective pro-
phylaxis and transfusion of blood products were in accor-
dance with institutional standardized operating procedures
and did not change during the study period.
A total of 178 patients were included. There were 97
(54%) patients in the early and 81 (46%) in the late G-CSF
initiation cohorts. Demographic and disease-specific char-
acteristics are depicted in Table 1. Both cohorts were matched
with respect to age, sex, diagnosis, stem cell mobilization
method, plerixafor administration, conditioning regimen, and
disease status prior to stem cell transplantation (Table 1).
Median infused CD34+ cell dose was higher in the late
G-CSF cohort (4.259 × 10
6
/kg vs. 3.808 × 10
6
/kg, p = 0.047).
Median time to neutrophil engraftment was significantly
shorter in early G-CSF initiation cohort (10 [6–13] days vs.
* Marcos de Lima
Marcos.delima@uhhospitals.org
1
Stem cell Transplant Program, University Hospitals of Cleveland
Seidman Cancer Center, Case Western Reserve University,
Cleveland, OH, USA
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