Frank Firkin1, Fernando Roncolato2, Wai Khoon Ho3. 1. Department of Medicine, St Vincent's Hospital, Melbourne University, Fitzroy, Vic., Australia. 2. Department of Haematology, St George Hospital, Kogarah, NSW, Australia. 3. Department of Haematology, Austin Hospital, Heidelberg, Vic., Australia.
Abstract
OBJECTIVE: To determine the potential for arsenic trioxide (ATO) to be safely and effectively incorporated into induction therapy of newly diagnosed acute promyelocytic leukaemia (APL) in patients with severe chronic renal failure (CRF) by reduction of the ATO dosage to compensate for reduced renal elimination of arsenic in CRF. PATIENTS AND METHODS: Two of the four CRF patients with APL in the study were dialysis-dependent, and two had eGFRs of 18 and 19 mL/min/1.73 m(2) . ATO dosage schedules were adjusted to obtain comparable whole-blood arsenic levels to those in APL patients with normal renal function who achieved molecular remission (MR) while receiving 10 mg ATO daily for 28 d. RESULTS: Average ATO administered per day in CRF patients ranged from 36 to 50% of the ATO administered to APL patients with normal renal function. No clinically significant cardiac, hepatic or other toxicities were detected. RT-PCR-negative MR was achieved after one treatment course in two patients and after two courses in the others. Relapse-free survival is 155, 60, 43 and 5 months. CONCLUSION: The observations in this pilot study have demonstrated whole-blood arsenic levels can provide a guide to adjustments of ATO dosage schedules that permit safe and effective therapeutic outcomes in APL patients with severely compromised renal function.
OBJECTIVE: To determine the potential for arsenic trioxide (ATO) to be safely and effectively incorporated into induction therapy of newly diagnosed acute promyelocytic leukaemia (APL) in patients with severe chronic renal failure (CRF) by reduction of the ATO dosage to compensate for reduced renal elimination of arsenic in CRF. PATIENTS AND METHODS: Two of the four CRF patients with APL in the study were dialysis-dependent, and two had eGFRs of 18 and 19 mL/min/1.73 m(2) . ATO dosage schedules were adjusted to obtain comparable whole-blood arsenic levels to those in APLpatients with normal renal function who achieved molecular remission (MR) while receiving 10 mg ATO daily for 28 d. RESULTS: Average ATO administered per day in CRF patients ranged from 36 to 50% of the ATO administered to APLpatients with normal renal function. No clinically significant cardiac, hepatic or other toxicities were detected. RT-PCR-negative MR was achieved after one treatment course in two patients and after two courses in the others. Relapse-free survival is 155, 60, 43 and 5 months. CONCLUSION: The observations in this pilot study have demonstrated whole-blood arsenic levels can provide a guide to adjustments of ATO dosage schedules that permit safe and effective therapeutic outcomes in APLpatients with severely compromised renal function.
Authors: Nathaniel Holcomb; Mamta Goswami; Sung Gu Han; Tim Scott; John D'Orazio; David K Orren; C Gary Gairola; Isabel Mellon Journal: DNA Repair (Amst) Date: 2017-02-16
Authors: S Masciarelli; E Capuano; T Ottone; M Divona; S De Panfilis; C Banella; N I Noguera; A Picardi; G Fontemaggi; G Blandino; F Lo-Coco; F Fazi Journal: Leukemia Date: 2017-08-04 Impact factor: 11.528