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An Overview of Drug-Induced Nephropathies *
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
Jean Paul Fillastre, Michel Godin
This drug has been widely used to treat hematologic malignancies and a variety of solid tumors. The nephrotoxicity of cyclophosphamide is limited to impairment of water excretion after high-dose therapy (50 mg/kg body weight). Impaired water excretion induced hyponatremia. This abnormality appeared very quickly within 12 h post dose and resolves generally within 24 h after drug withdrawal. Cyclophosphamide has a direct toxic effect on the renal tubular cells of the distal nephron and collecting duct, facilitating increased water reabsorption. This syndrome is generally mild, but on one occasion it resulted in the death of a patient from cerebral edema (Harlow, 1979). Hemorrhagic cystitis is another very well-known complication of the drug.
Lesch–Nyhan disease and variants
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Another presentation is with painless hematuria in a pattern that suggests a diagnosis of hemorrhagic cystitis or glomerulonephritis (Figure 65.15) [29]. Cystourethography in this patient led to transient hypertension, oliguria, and azotemia; following anesthesia and renal biopsy, oliguria/anuria recurred, and the BUN (blood, urea, nitrogen) rose to 80 mg/dL.
Intense Immunosuppression Followed by Autologous Stem Cell Transplantation in Severe Multiple Sclerosis Cases
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
G.L. Mancardi, R. Saccardi, A. Murialdo, F. Pagliai, F. Gualandi, A. Marmont, M. Inglese, P. Bruzzi, M.P. Sormani, M.G. Marrosu, G. Meucci, L. Massacesi, A. Bertolotto, A. Lugaresi, E. Merelli, M. Filippi
Mobilization was successful in all cases and generally well tolerated and a median number of 9.06 × 106/kg of CD34+ cells were collected (range 3.51-26.02 × l06/kg). However, adverse effects were observed in some cases: one patient experienced subclavian phlebitis, one transient inappropriate secretion of ADH and a third hemorrhagic cystitis. This last patient (n 13) was treated in the previous year with CY 1 gr. IV every month for 6 months, without significant clinical results. The hemorrhagic cystitis was severe and lasted almost 2 months. Nadir of polymorphonuclear cells (PMN) occurred 8 days after mobilization (range 7-11 days) and of platelets (Pit) on day 10 (range 3-13). Median days with PMN<0.5 × l09/L and Plt<50 × l09/L were 4 (range 2-4) and 0 (range 0-4), respectively.
Outcomes and risk factors of hemorrhagic cystitis in pediatric allogeneic hematopoietic stem cell transplantation recipients using different graft source and condition with severe aplastic anemia
Published in Hematology, 2022
Bohan Li, Lijun Meng, Yuanyuan Tian, Qin Lu, Li Gao, Peifang Xiao, Jun Lu, Jie Li, Lin Wan, Zhiheng Li, Shaoyan Hu, Lingjun Kong
Hemorrhagic cystitis was defined as microscopic or macroscopic hematuria and dysuria with a negative bacterial culture in the urine and no other hemorrhagic conditions. The symptoms of HC are classified as follows: grade 1 shows microscopic hematuria; grade 2, macroscopic hematuria; grade 3, macroscopic hematuria with clots, and grade 4, macroscopic hematuria with clots, urinary obstruction, kidney damage, and bladder damage [18]. Overall survival (OS) was considered as time from allo-HSCT to death. Neutrophil engraftment was defined as achieving an absolute neutrophil count ≥0.5 × 109/L for 3 consecutive days. Platelet engraftment is defined as achieving a platelet count ≥20 × 109/L without transfusion support for 7 consecutive days. Myeloablative conditioning regimen, defined as busulfan (BU) >8 mg/kg. The diagnosis and grading of acute GVHD (aGVHD) and chronic GVHD (cGVHD) were assigned by the transplant center using standard criteria [19,20]. Engraftment syndrome (ES) was defined as fever in absence of infection, skin rash, diarrhea, capillary leak syndrome, and pulmonary injury which occur before or during neutrophil engraftment [21].
A review of the risks of long-term consequences associated with components of the CHOP chemotherapy regimen
Published in Journal of Drug Assessment, 2022
Crystal Watson, Hemanth Gadikota, Arie Barlev, Rachel Beckerman
Four studies were included, notably these studies were older with all four pre-dating 199864–67. Three studies reported the prevalence of bladder cancer64,65,67 and three studies described hemorrhagic cystitis in cancer patients that were exposed to cyclophosphamide64–66 (Table 2). The onset of bladder cancer following cancer treatment ranged from 5 to 8.5 years (the duration of follow-up in identified studies ranged from 4 to 17 years). The risk of bladder cancer significantly increased with increasing dose of cyclophosphamide, with a 6 (95% CI: 1.3–2.9) and 14.5 (95% CI: 2.3–94)‐fold increased risk at cumulative doses of 20‒49 g and ≥50 g, respectively; risks also increased with duration of treatment with a 3.7 (95% CI: 0.6–22)-fold and 11.8 (95% CI: 2.3–61)-fold increased risk for 1–2 years and ≥2 years of treatment67 (Table 3).
An update on the safety of treating relapsing-remitting multiple sclerosis
Published in Expert Opinion on Drug Safety, 2019
Clara G. Chisari, Simona Toscano, Emanuele D’Amico, Salvatore Lo Fermo, Aurora Zanghì, Sebastiano Arena, Mario Zappia, Francesco Patti
Cyclophosphamide (CYC) is an alkylating agent, determining a cytostatic effect on proliferating T and B-lymphocytes and inducing a shift versus a Th2-immune response [218]. Despite no improvement in long-term disability progression has been reported [219], studies among RRMS patients detected a reduction or stabilization of relapse rate and MRI outcomes, with EDSS stabilization or improvement [220–223]. It is usually administered i.v. with a pulse regimen, starting with a dose of 800 mg/m2 every 4–8 weeks for 12–24 months. Dose may be fixed or augmented in order to obtain a target leukocyte count of 3000/mm3 and a lymphocyte count of 800/mm3. Induction regimen may be also employed administering 600 mg/m2 on days 1, 2, 4, 6, 8 for 8 days and then 600 mg/m2 every 4–6 weeks according to absolute leukocyte count [224]. Data from clinical trials reported alopecia, nausea and vomiting, transient myelosuppression, amenorrhea and azoospermia as common AEs. Besides, in up to 4.5% of CYC-treated patients, hemorrhagic cystitis has been reported [225,226]. An increased risk of bladder cancer has been assessed in 5.7% of chronically catheterized CYC-treated patients [227]. Myelodysplastic syndromes, lymphoma, thyroid cancer, and sarcoma can occur, even after several years from the last administration [225]. Women of childbearing age and men should use adequate contraception during treatment, which exerts teratogen effects and should be discontinued during pregnancy and breastfeeding.