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Melphalan (M) 200 mg/m2 and 140mg/m2, is the standard conditioning regimen for multiple myeloma (MM) patients (pts) with normal renal function (NRF) and abnormal renal function(AbrF) respectively, undergoing autologous stem cell transplant (ASCT).In an effort to escalate the dose of M and to improve the efficacy, we designed a dose-escalation study of M in conjunction with cytoprotective palifermin(P).Pts were stratified according to their renal function and enrolled independently in this dose escalation phase Ⅰ study.Eligibility criteria: creatinine clearance≤60ml/min/1.73 m2 for NRF and>60 for AbrF, age>18 years, no dialysis, no active OM and a suitable candidate for ASCT.M dose ranged from 200-280 mg/m2 (NRF arm) & 140-200 mg/m2 (AbrF arm).M dose escalated at the increment of 20 mg/m2.Six dosages of P 60 mcg/kg/d were given I.V between day-5 to day+3.Dose escalations were to stop if dose-limiting toxicities (DLTs) occurred at M dose in ≥2/3 pts, with that dose declared as the maximal administered dose and the level below where<1/6 pts had DLTs was considered maximum tolerated dose (MTD).Grade 4 oral mucositis (OM),grade 4 diarrhea and>grade 3 cardiac toxicity were considered DLT for M.Improvement in the incidence and severity of OM was the experimental objective for this study.The grade of OM was assessed daily by a clinician according to the World Health Organization oral-toxicity scale (grade 0-4).NRF Arm: Of 18 evaluable pts there was no treatment related deaths by day 100.The median age was 48.5 (33-65).The most common adverse events related to P included rash (18 events, no≥grade 3events), elevation of amylase (10 events, 4 were grade 3 but asymptomatic) and lipase (5 events, 2 were grade 3 but asymptomatic), edema (11events, no≥grade 3).The overall incidence of OM grade 3 was 44% (8/18) with a median duration of 10 days (range 4-20 days).Eleven patients (61%) required opioid analgesics.None of the patients received TPN/NG feeding.Two out of six pts that were given M 280 mg/m2 did not develop any OM.Cardiac toxicity (DLT) in the form of atrial fibrillation did occur in one of six patients treated with M 280 mg/m2.AbrF Arm: Data on 15 evaluable pts is reported as 4 pts were removed.Median age was 59 years (36-67y).The overall incidence of OM grade 3 was 53% (8/15) and a median duration of ≥grade 3OM was 6.5 days (3-42).One patient in L2 (M 160 mg/m2) developed atrial fibrillation on Day+9.Two pts in L4 (M 200mg/m2) developed grade 4 OM, hence reaching DLT.No DLT was observed in 6 pts enrolled in L3 (M 180mg/m2).Conclusion: P has permitted safe dose escalation of M up to 280 mg/m2 in NRF and 180 mg/m2 in AbrF arms with acceptable toxicity.