Feasibility of Administering High-Dose Melphalan (HDM) with Autotransplantation in Myeloma Patients on Dialysis.

Bhawna Sirohi, Ray Powles, Samar Kulkarni, Anna Menon, Tanya Ahmed, Radovan Saso, Shama Goyal, Claudius Rudin, Jenny Treleaven.

Author address: 

Leukaemia & Myeloma Unit, Royal Marsden Hospital, Surrey, United Kingdom


The improvement in outcome for patients with myeloma and renal failure has partly been attributed to the availability of renal replacement therapy, however limited data are available on the feasibility of giving HDM to patients on dialysis. Between 3/99 and 8/01, 6 myeloma patients on dialysis (50-65 years, median 60; 5 male, 1 female) with a median 51Cr-EDTA glomerular filtration rate of 12 (range 4-18 mL/min/m2 ) received high-dose melphalan (HDM) (4: 200 mg/m2, 2: 140 mg/m2). 5 had light-chain disease and 1 had IgG disease (3 k, 3 l). All had renal failure at diagnosis. Initial therapy was 2-6 courses (median 6) of infusional C-VAMP (cyclophosphamide, vincristine, doxorubicin, methylprednisolone) without dose-modification to which 3 had partial response (PR) and 3 had no response (NR). Serum creatinine at the time of HDM was 5.1-8.3 mg/dL (median 7.2). At the time of HDM, 4 patients were on hemodialysis (HD), 1 was about to start HD (had an arteriovenous (AV) fistula installed and received haemofiltration throughout the peri-transplant period), and 1 was on continuous ambulatory peritoneal dialysis. All patients received renal replacement therapy throughout the post-transplant period in addition to G-CSF starting on day +4. 1.2-6.5 (median 2.14) x 106 CD34+ cells/kg were infused. The time to 0.5 x 109/L neutrophils was 12-16 (median 14) days. All patients had grade III-IV mucositis, and 4 had microbiologically-confirmed infections. Atrial fibrillation (AF) was seen in 4 patients 3-9 days after the transplant. 3 of 4 patients receiving 200 mg/m2 melphalan (Mel200) died of toxicity at 3-4 weeks (sepsis in 2, stroke in 1) compared with 0 of 2 receiving 140 mg/m2(Mel140) All 3 dying of toxicity were NR at the time of HDM and had progressive disease. Of the 3 surviving patients (all in PR at the time of HDM), 2 attained CR and 1 remained in PR. Both the patients who attained CR changed over from thrice weekly HD to twice weekly HD which is important for good quality of life and the patient in PR did not commence HD at all (the AV fistula was closed). But, the two patients who received Mel140 have both relapsed at 8 (started HD )and 20 months (switched to thrice weekly HD) post HDM. The patient in CR after Mel200 remained in CR and died possibly of pulmonary aspergillus 22 months post HDM. Both the relapsed patients received Mel140 the second time around- 1 died of septicaemia and progressive myeloma ; 1 is day + 43 post Mel140 and recovering well. Even though severe renal dysfunction at the time of HDM is associated with an increased rate of complications in myeloma patients [Sirohi et al, Blood 2000 : 96;1675a], these high-risk patients do benefit from HDM with improvement in quality of life. An optimum dose of melphalan between Mel140 and Mel200 needs to be determined.

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Full conference title: 

43rd American Society of Hematology (ASH) Annual Meeting
    • ASH 43rd (2001)