The Goldilocks conundrum: how much granulocyte colony-stimulating factor following autologous stem cell transplant is ‘just right’?

It is tempting to assume that faster granulocyterecovery following high dose chemotherapy andautologous stem cell transplant (ASCT) will resultin enhanced patient outcomes of fewer infections,less antibiotic usage, more rapid resolution ofmucositis, and faster discharge from hospital, withall of the cost savings that would naturally followfrom such outcomes.The use of granulocyte colony-stimulating factor(G-CSF) following ASCT does indeed result infaster neutrophil recovery of approximately 2 days inmany reported series, as reviewed by Ojeda et al. [1]. However, despite this, studies have been inconsistentin showing that routine use of G-CSF providesadvantages such as reductions in antibiotic use andhospitalization days and improved cost-effectiveness.Acknowledging the obligatory period of neutropeniaprior to the engraftment of granulocytic precursors inASCT, some investigators have studied the use ofdelayed G-CSF administration post-transplant, andhave shown that despite later commencement andless total G-CSF use there was no erosion of clinicaladvantage [2–5]. Despite the variation observed inclinical outcome in these studies there remainssome confusion regarding the value of routine useof G-CSF post-ASCT, a situation reﬂected in thepositive recommendation for routine G-CSF usepost-ASCT by the American Society of ClinicalOncology (ASCO) guidelines [6], but a lowerrecommendation in the European Society for Med-ical Oncology (ESMO) guidelines [7]. In recent years, the availability of a pegylatedpreparation of G-CSF has logically led to theinvestigation of its utility for the support of neutro-phil engraftment following ASCT. In this issue ofLeukemia and Lymphoma, Wanneson and col-leagues report their experiences of post-ASCToutcomes in relatively uniformly treated populationsof patients undergoing ASCT for either myeloma orlymphoma, comparing pateints treated with pegy-lated (Peg)-G-CSF to a matched cohort of patientswho received standard-of-care G-CSF on eitherdayþ5 or dayþ7 [8]. Their results indicate that Peg-G-CSF administra-tion did indeed result in more rapid neutrophilrecovery, by approximately 1.5 days, 2 days lessantibiotic use, and a shortening of duration of in-hospital stay by 1 day. The size and retrospectivenature of this cohort analysis precluded performing ameaningful cost–beneﬁt analysis, although it isunlikely that, at current drug costs, an overall costsaving would probably have been observed. Whilstthe clinical improvements were assumed to reﬂectfaster neutrophil engraftment, it remains possible thatthe improved outcomes were a result of a Peg-G-CSFinduced increase in the pre-nadir neutrophil num-bers, resulting in an overall shorter time with severeneutropenia. Overall, the ﬁndings from Wannesonet al. suggest that the biological effect of a single doseof Peg-G-CSF from dayþ1 post-ASCT is similar orslightly enhanced to that delivered by daily G-CSF.This is a ﬁnding in line with that observed in otherstudies of Peg-G-CSF administration followingASCT [9,10]. One important ﬁnding from the Wanneson analysisis that patients undergoing ASCT for differentindications (myeloma vs. lymphoma) may experiencedifferent levels of advantage from post-ASCT G-CSFadministration. Patients with multiple myeloma re-ceiving dayþ1 Peg-G-SCF post-ASCT experienced