IntroductionLate cardiotoxicity is a known complication of anthracycline therapy but the long-term effects of low cumulative doses are not well documented. We studied late cardiotoxicity in survivors of childhood acute lymphoblastic leukemia (ALL) treated with low anthracycline doses 10 to 20 years earlier.MethodsSeventy-seven ALL survivors who received a cumulative anthracycline dose <250 mg/m² and were at least 10 years after treatment were evaluated for signs of clinical heart failure. Cardiac function was assessed by echocardiography including tissue Doppler measurements of the septal mitral annulus in 37 ALL survivors 10.6–18.3 years (median 13.3 years) after anthracycline treatment with cumulative doses of 180 (n = 19) or 240 mg/m² (n = 18). The control group consisted of 30 healthy volunteers matched for age, sex, BSA, and BMI.ResultsNo clinical relevant cardiotoxicity was found. Left ventricular shortening fraction (SF) was significantly reduced in male ALL survivors. Three of the 19 male ALL survivors had an SF below 30%. Male ALL survivors showed a significantly lower early filling velocity to atrial contraction velocity ratio but myocardial velocity during early filling was comparable between patients and controls. ALL survivors had a significantly longer isovolumetric relaxation time (IVRT). Thirty percent of the ALL survivors have an abnormal IVRT compared to the normal range of the controls.Conclusion and implications for cancer survivorsAt a median of 13.3 years after exposure to cumulative doses of anthracyclines of 180 or 240 mg/m², no clinical relevant cardiotoxicity was found but subclinical cardiac abnormalities were present in 30% of the patients.
Acute lymphoblastic leukemia was diagnosed in a 7-year-old girl. Two months after insertion of a central venous catheter, she developed fever and complained of headache and abdominal pain. Physical examination revealed no focus of infection. A gram-negative nonfermenting bacillus was recurrently cultured from blood. Extensive biochemical testing and 16S ribosomal DNA sequencing led to the identification of Ralstonia gilardii. CASE REPORTAcute lymphoblastic leukemia (ALL) was diagnosed in a 7-year-old girl in May 2000, and treatment was initiated according to the EORTC-CLCG-58951 protocol for children with very-low-risk ALL. The girl achieved hematologic remission after induction chemotherapy. A central venous catheter was inserted in June 2000. The girl tolerated the treatment uneventfully until September 2000, when, during a course of chemotherapy (high-dose methotrexate), she developed spiking fever as high as 40°C. She complained of headache and abdominal pain and vomited twice. Physical examination revealed no focus of infection. The leucocyte count was 5,800/ml, with an absolute neutrophil count of 4,760/ml and elevated C-reactive protein (87 mg/dl). The chemotherapy was stopped, and the girl was treated with intravenous (i.v.) ampicillin (100 mg/kg of body weight/day). One day later blood cultures grew gram-negative bacilli, and (i.v.) netromycin (7.5 mg/kg/day) treatment was added. The spiking fever disappeared and the girl's health improved.A gram-negative nonfermenting bacillus was isolated and found to be resistant to ampicillin, piperacillin, aztreonam, gentamicin, and tobramycin and susceptible to cefuroxime, ceftriaxone, ceftazidime, imipenem, co-trimoxazole, ofloxacin, and amikacin. The girl was treated as an outpatient with i.v. ceftriaxone (100 mg/kg/day) once daily for 4 more days. Thirtysix hours after the ceftriaxone treatment was stopped, she again developed spiking fever, and i.v. ceftriaxone (100 mg/kg/ day) was restarted in combination with i.v. amikacin (15 mg/ kg/day). Again, a gram-negative nonfermenting bacillus was cultured from blood. The girl showed an allergic reaction to ceftriaxone with rash and pruritus, and the ceftriaxone was replaced with i.v. ciprofloxacin (20 mg/kg/day). The spiking fever disappeared again, and amikacin and ciprofloxacin i.v. treatment was given for 7 more days. Blood cultures remained negative, and the central venous catheter was not removed. Three months later the intensive chemotherapy was completed and the girl was doing well. The catheter was removed on January 8 2001. No nonfermenting gram-negative bacilli were cultured from the tip.Discussion. The gram-negative bacillus was isolated in pure culture from all eight FAN aerobic blood cultures and from one of the eight BacT/Alert anaerobic cultures (Organon Teknika, Turnhout, Belgium), collected over a period of 10 days. Initial identification based on the API20NE system (bioMérieux, Marcy l'Etoile, France) yielded code 1000474, leading to an identification as Alcaligenes faecalis, Comamonas acidovorans ...
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Given that IQ scores did not decline, our findings demonstrate a stable pattern. However, the lower PIQ scores at baseline may indicate that performance functioning is vulnerable to acute neurotoxicity. Also, lower scores for younger patients highlight the stronger impact of the disease and/or treatment at younger age.Copyright © 2016 John Wiley & Sons, Ltd.
. Out of 108 patients, 78% achieved complete remission (CR), and event-free survival (EFS) and survival rates (s.e., %) at 7 years were 40 (5) and 51% (6%), respectively. It indicated that mitoxantrone could be substituted for conventional anthracyclines in the treatment of childhood AML without inducing cardiotoxicity. The aim of the next EORTC 58921 trial was to compare the efficacy and toxicity of idarubicin vs mitoxantrone in initial chemotherapy courses, further therapy consisting of allogeneic bone marrow transplantation (alloBMT) in patients with an HLA-compatible sibling donor or chemotherapy in patients without a donor. Out of 177 patients, recruited between October 1992 and December 2002, 81% reached CR. Overall 7-year EFS and survival rates were 49 (4) and 62% (4%), respectively. Out of 145 patients who received the first intensification, 39 had a sibling donor. In patients with or without a donor, the 7-year disease-free survival (DFS) rate was 63 (8) and 57% (5%) and the 7-year survival rate was 78 (7) and 65% (5%), respectively. Patients with favorable, intermediate and unfavorable cytogenetic features had a 5-year EFS rate of 57, 45 and 45% and a 5-year survival rate of 89, 67 and 53%, respectively.
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