Impact of transfusion burden prior to SCT on OS & NRM post-SCT: GITMO

Patients with myeloid malignancies undergoing allo-SCT

Charts - Impact of transfusion burden
Table. Studies examining an impact of reducing IOL around SCT for hematologic malignancies.
Time of intervention Study type SCT type N Disease type IOL measure Intervention Endpoints Reference
Pre-SCT Retro Allo NOS 101 Multiple Pre SF DFO TRM, EFS, OS p≤0.001 for all Lee 2009
Pre-SCT Pro MA 5 AML, MDS SF >1000
LIC >5 		DFO Closed for slow accrual Armand 2013
Post-SCT Pro Allo + ASCT 10 SF Phleb Improved LFT’s in most1 McKay 1996
Post-SCT Pro Allo NOS 38 Multiple SF
LIC by MRI 		Phleb (n=29) 10/16 normalized AST/ALT Rose 2007
Post-SCT Pro Allo NOS 20 Multiple SF >1000
LIC by MRI 		Phleb SF decreased (p=0.0001)
LIC decreased (p=0.0003) 		Kew 2015
Post-SCT Pro MA, NMA 23 Multiple LIC by MRI Phleb (n=8), ICT (n=3) Phleb — liver disease (n=3), CHF (n=1), all improved
ICT — all LIC improved
Observation — 4 of 5 had decrease in SF over time 		Majhail 2010
Post-SCT Pro MA, RIC 42 Multiple SF>1000
LIC by SQUID 		Phleb (n=19) LIC improved (p<0.001)
LFT improved (p≤0.027)
IFI, p=0.006 		Busca 2010
Post-SCT NS Allo NOS 6 Myeloid LIC by biopsy;
severe IOL in 4 		EPO-assisted phleb SF normal @ 11 mo
LFT normal @ 7 mo
4 able to d/c IS for GVH 		Kamble 2006
Post-SCT Pro Allo NOS 23 Multiple SF
liver bx 		Phleb or DFO Improved SF
Improved LFT’s 		Tomas 2000
Post-SCT NS Allo NOS 143 Multiple SF >2000
no infection increased LFT
LIC by MRI 		DFO MVA: DFO >2mo decreased RI (p=0.01) including in advanced disease (p=0.03)
improved DFS (p=0.01) 		Kaloyannidis 2010
Post-SCT Pro Allo NOS 76 AML, MDS2 SF >1000
CRP <10 		DFX 10 mg/kg/d, adjusted; until SF <500 or EOS SF decreased (p<0.0001)
7.5 mg/kg/d best-tolerated
AE similar to non-SCT 		Jaekel 2016
Post-SCT Pro Allo NOS 30 Multiple ≥6mo post SCT DFX 10 mg/kg/d x52 wk or to normalized SF AE as expected Vallejo 2014
Post-SCT Retro MA, NMA 80 Multiple SF post ≥1000 DFX vs phleb MVA: OS favored DFX 0.023 Sivgin 2013
Post-SCT Pro Allo NOS 8 AL, AA Engrafted,
Hb <LLN, TD 		DFX Median time to TI 23d following start of DFX Visani 2014
1numbers not given 2predominantly. AA, aplastic anemia; AE, adverse events; AL, acute leukemia; Allo, allogeneic; ALT, alanine aminotransferase; AML, acute myeloid leukemia; ASCT, autologous stem cell transplantation; AST, aspartate aminotransferase; bx, biopsy; CHF, congestive heart failure; CRP, C-reactive protein; d, days; d/c, discontinue; DFO, deferoxamine; DFS, disease-free survival; DFX, deferasirox; EFS, event-free survival; EOS, end of study; EPO, erythropoietin; GVH, graft versus host; Hb, hemoglobin; ICT, iron chelation therapy; IFI, invasive fungal infection; IOL, iron overload; IS, immunosuppression; LIC, liver iron concentration; LFT’s, liver function tests; LLN, lower limit of normal; MA, myeloablative; MDS, myelodysplastic syndrome; mo, months; MRI, magnetic resonance imaging; NMA, non-myeloablative; MVA, multivariate analysis; n, number; NOS, not otherwise specified; NS, not specified; OS, overall survival; phleb, phlebotomy; pro, prospective; retro, retrospective; RI, relapse incidence; RIC, reduced intensity conditioning; SCT, stem cell transplantation, SF, serum ferritin; SQUID, Superconducting Quantum Interference Device; TD, transfusion dependent; TI, transfusion independent; TRM, transplant-related mortality; wk, weeks. Leitch HA, et al. Crit Rev Oncol Hematol. 2017;113:156-170.

Iron chelation therapy prior to SCT improves survival (n=101)

Charts - Iron chelation therapy prior to SCT improves survival (n=101)