Sequential administration of sargramostim and filgrastim in pediatric allogeneic stem cell transplantation recipients undergoing myeloablative conditioning^†

Abstract

G-CSF and GM-CSF both hasten myeloid engraftment post-MA-alloSCT; however, GM-CSF is earlier acting and less expensive. The objective was to evaluate efficacy/safety of sequential administration of GM-CSF followed by G-CSF in children post-MA-alloSCT. From January 2001 to June 2005, 31 children received 32 MA-alloSCT: mean age 6.65 yr; MRD BM or PBSC vs. related or unrelated UCB 11:21; malignant vs. non-malignant disorders 22:10. GM-CSF (250 microg/m(2) IV QD) began on day of stem cell infusion. GM-CSF was switched to G-CSF (10 microg/kg IV QD) when WBC >or= 300/mm(3) x 2 days. G-CSF continued until ANC >or= 2500/mm(3) x 2 days, then tapered to maintain ANC >or= 1000/mm(3). Median time to myeloid engraftment (ANC >or= 500/mm(3) x 3 days) was 17 days [13 days vs. 24 days, MRD BM/PBSC vs. UCB (p < 0.0001)], occurring at a median time of two days after switch to G-CSF. Clinically relevant adverse events were bone pain (n = 8) and large pleural effusion (n = 1). It was estimated that sequential GM-CSF/G-CSF was cost-effective compared with G-CSF alone [cost-savings of $1311/patient ($41,952/study), 2007 Red Book Average Wholesale Price]. In summary, it was demonstrated that sequential administration of GM-CSF/G-CSF post-MA-alloSCT was safe, cost-effective and resulted in prompt myeloid engraftment.

A pilot study of reduced toxicity conditioning with BU, fludarabine and alemtuzumab before the allogeneic hematopoietic SCT in children and adolescents

“…17,25 Thirdly, faster implementation of growth factors, which were started at day 0 in our study, whereas day þ 21 in the Horn et al study. 9 As sequential administration of GM-CSF/G-CSF post-myeloablative AlloHSCT was safe, and resulted in prompt myeloid engraftment, 19 this can possibly contribute to more sustained engraftment. Fourthly, the dose of BU was twofold higher than in the study by Horn et al, 9 providing stronger immunosuppression.…”

“…or subcutaneously until an ANC of X2500/mm 3 was achieved for 3 days as we described previously. 19 Herpes simplex prophylaxis consisted of acyclovir (250 mg/m 2 ) i.v. three times a day from day þ 5 until engraftment and pgrade II mucositis.…”

Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease

“…21,22 Tacrolimus 0.03 mg/kg/day continuous i.v. infusion or 0.12 mg/kg orally (PO) twice a day was started (dose adjusted to maintain blood levels of 10-20 ng/mL) on day − 8.…”

“…or subcutaneously until an ANC ⩾ 2.5 × 10 9 /L was achieved for 3 days. 22 Herpes simplex prophylaxis was acyclovir (250 mg/m 2 ) i.v. q8 h from day − 5 until engraftment.…”

Safety of liposomal cytarabine CNS prophylaxis in children, adolescent and young adult hematopoietic stem cell transplant recipients with acute leukemia and non-Hodgkin lymphoma

“…Acute GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil with dosage adjustment to maintain safe and therapeutic blood levels and utilized standard supportive care measures as we have previously described. [8][9][10] All patients developing ⩾ Grade II acute GVHD received systemic corticosteroid therapy (minimum equivalent 2 mg/kg of prednisone per day). Commercial supply of liposomal cytarabine (DepoCyt, Sigma-Tau Pharmaceuticals, Inc, Gaithersburg, MD, USA) was utilized from single-use 5-mL vials containing 50 mg (10 mg/mL) each.…”