Deferred Dosing of Granulocyte Colony Stimulating Factors in Autologous Hematopoietic Transplantation for Multiple Myeloma

In autologous hematopoietic stem cell transplantation (ASCT), G-CSF administered from day +7 until ANC recovery, expedites ANC recovery and reduces days of hospitalization by 1-2 days.  To determine whether delayed and abbreviated G-CSF dosage could produce equivalent ANC recovery and thereby improve cost effectiveness of ASCT for myeloma, we delayed administration of G-CSF until WBC recovery had begun and was ≥0.20/uL. G-CSF so administered was labeled deferred G-CSF dosing (DGD), Patients in the conventional dosing group (CGD) received daily doses of 5 mg/kg G-CSF beginning day +7. The primary and secondary end points are listed in table-1. The Institutional Review Board approved retrospective chart analysis.

A total of 117 patients with multiple myeloma received ASCT from January 2005 to September 2012. Of these, 65 patients received DGD and 52 received CGD.  Patient, disease, and transplant-related variables were similar between 2 groups; patients in DGD received a larger dose of CD34+ cells/kg (median 4.49, range= 2.49-10.2 vs. median 3.79, range= 2.61-9.42, p= 0.021)

The CGD group received a median of 5 doses of G-CSF, while the DGD group received, a median of 0 (range 0-5, p=<0.0001) G-CSF doses (5μg/kg) when the WBC were a median of 1.18/uL (range 0.20/uL -2.54/uL) and the ANC a median of 158/uL (range 0-1168/uL); 36/65 (55%) patients in DGD received no G-CSF (at physician's discretion) and those who received the drug did so starting on day 14 (median) post-transplant (range =11d-18d). There was no difference in the incidence or duration of ≥ grade III mucositis, weight gain, rash or engraftment syndrome between DGD and CGD groups. However, as shown in Table 1 the CGD group had significantly faster engraftment, abbreviation of neutropenia, diminished antibiotics use, and shorter hospitalization. These effects were independent of CD 34 cell dose. Primarily because of abbreviated hospital stay, there was a 17% cost benefit to the use of CGD, supporting the overall benefit of this treatment regimen for patients with MM who receive ASCT.

Characteristics                                                 CGD group                 DGD group     P value

 

Neutrophil Engraftment (days)                       12 (11-14)                   15 (11-20)       <0.0001

Duration of neutropenia                                  7 (5-9)                         10 (6-16)         <0.0001

(ANC <500)

Duration of severe neutropenia                       6 (4-9)                         8 (4-10)           <0.0001

(ANC < 100) days

Duration of intravenous antibiotics                5 (3-20)                       8(3-15)            0.016

                                               

Duration of hospital stay                                17 (14-24)                   19 (16-28)        <0.0001