High-Dose Chemotherapy without Stem Cell Transplantation for Refractory Childhood Systemic Lupus Erythematosus

Abstract

Background:Intensive chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) is effective for refractory systemic lupus erythematosus (SLE). When intensive chemotherapy is immunoablative but nonmyeloablative, ASCT for hematopoietic reconstitution, with the risk of reinfusing autoreactive lymphocytes, is unnecessary. Methods:Four children aged 12–16 years were enrolled, 3 with WHO class IV nephritis, 2 with hemolytic anemia and 1 with thrombocytopenia. Median disease duration prior to the study was 4 years (range 1–6). Previous therapy, including intravenous bolus cyclophosphamide (Cy) with a median accumulated dose of 6.5 g/m² and high-dose methylprednisolone with a median accumulated dose of 370 mg/kg, had failed. The protocol included: Cy 1.2 g/m² daily for 4 days, fludarabine 30 mg/m² daily for 4 days, porcine antilymphocyte globulin 25 mg/kg daily for 3 days. Results:Themedian duration of absolute neutrophil count <0.5 × 10⁹/l was 5.5 days after treatment. The median SLE Disease Activity Index and urine protein decreased from 8.5 and 3.4 to 1.0 and 0.1 g/day at the date of last follow-up (median 20 months), respectively. Two cases with hemolytic anemia and 1 with thrombocytopenia before treatment recovered to normal or near normal hemogram, respectively. All patients achieved complete or partial remission within 10–28 months of follow-up. Conclusion:Intensive chemotherapy leads to rapid hematopoietic reconstitution without ASCT and appears beneficial in refractory childhood SLE. Further study is needed.

Role of carnitine in cancer chemotherapy-induced multiple organ toxicity

“…Carnitine and oxazaphosphorines-induced organs toxicity Cyclophosphamide (CP) and ifosfamide (IFO) are alkylating oxazaphosphorine agents that are commonly used in most cancer chemotherapy and immunosuppressive protocols (Murphy et al, 1986;Preiss and Baumann, 2001). Unfortunately, the optimal clinical usefulness of these drugs is severely limited by a high incidence of urotoxicity, cardiotoxicity and nephrotoxicity (Brock et al, 1982;Colvin, 1999;Ludeman, 1999;Luo et al, 2008). The metabolic pathway of oxazaphosphorines leads to formation of chloroacetyl-CoA, with subsequent depletion of the CoA-SH levels.…”

Aminoguanidine, a Selective Nitric Oxide Synthase Inhibitor, Attenuates Cyclophosphamide-Induced Renal Damage by Inhibiting Protein Nitration and Poly(ADP-Ribose) Polymerase Activation

“…CP has been in the clinic since the late 1950s and is still one of the most widely used drugs in cancer chemotherapy [1,2]. CP has a wide spectrum of clinical uses and it has been proved to be effective in the treatment of cancer and non-malignant disease states such as rheumatoid arthritis and refractory childhood systemic lupus erythematosus [3,4]. While both CP and ifosfamide have severe urotoxic side effects, only ifosfamide is thought to be nephrotoxic.…”

Progression of cyclophosphamide-induced acute renal metabolic damage in carnitine-depleted rat model

“…Cyclophosphamide (CP) and its structural analogue ifosfamide (IFO), oxazaphosphorine alkylating agents, are highly effective cytotoxic drugs against different types of human tumours and are commonly used in cancer chemotherapy protocols [1][2][3]. While both CP and IFO have severe urotoxic side-effects, only ifosfamide is thought to be nephrotoxic, causing tubular damage and resulting in Fanconi syndrome [4][5][6][7].…”