Pediatric Stem Cell Transplantation Unit, Dana Farber/Children's Cancer and Blood Disorders Center, Boston, MA, USA.
Pediatric Oncology Department, National Cancer Institute (NCI), Cairo University, Cairo, Egypt.
J Egypt Natl Canc Inst. 2020 Feb 18;32(1):9. doi: 10.1186/s43046-020-00024-6.
Treatment for malignant embryonal brain tumors in young children usually employs cycles of standardly dosed cisplatinum followed by high-dose carboplatinum-containing conditioning with single or tandem autologous stem cell rescue (HDC-ASCR). High-dose carboplatin is potentially nephrotoxic, and additive platinum exposure may acutely impact renal function. Aiming to determine if decrease in renal function during conditioning assessed prior to each carboplatin dose was associated with acute increases in creatinine, requirement for dialysis or transplant-related mortality (TRM). This was a retrospective study of consecutive patients with medulloblastoma (n = 15) / atypical teratoid/rhabdoid tumor (AT/RT, n = 5) receiving HDC-ASCR. Fifteen patients underwent 1 HDC-ASCR (carboplatin × 3 doses/ etoposide/ thiotepa) and 5 patients underwent at least 1 of 3 planned tandem HDC-ASCR (carboplatin × 2 doses/ thiotepa). Renal function was assessed by daily creatinine and nuclear medicine glomerular filtration rate (GFR)/ creatinine clearance before each carboplatin dose.
In this cohort of 20 patients, 3 had doses of carboplatin omitted due to decreases in GFR: 1 did not develop nephrotoxicity, 1 experienced nephrotoxicity without need for dialysis, and 1 required dialysis temporarily but recovered renal function. Two patients did not have GFR changes but developed post-ASCR renal failure requiring dialysis and TRM.
Daily assessment of renal function by GFR, prior each dose of carboplatin during HDC-ASCR, will help in protecting the kidney in heavily treated population of oncology/HSCT patients. Although the study had a small number of patients which is a major limitation of the study, but it points to a serious transplant-related morbidity and mortality. So, larger scale studies are needed to clarify the best approach to carboplatin dosing to insure the optimal balance between efficacy and toxicity.
小儿恶性胚胎脑肿瘤的治疗通常采用标准剂量顺铂联合大剂量含卡铂的预处理方案，随后进行单或串联自体干细胞挽救（HDC-ASCR）。大剂量卡铂具有潜在的肾毒性，且额外的铂类暴露可能会急性影响肾功能。本研究旨在确定在每次卡铂剂量前评估预处理期间肾功能的下降是否与肌酐急性升高、需要透析或移植相关死亡率（TRM）相关。这是一项连续接受 HDC-ASCR 的髓母细胞瘤（n=15）/ 非典型畸胎瘤/横纹肌样瘤（AT/RT，n=5）患者的回顾性研究。15 例患者接受了 1 次 HDC-ASCR（卡铂×3 剂量/依托泊苷/噻替哌），5 例患者至少接受了 3 次计划串联 HDC-ASCR（卡铂×2 剂量/噻替哌）中的 1 次。在每次卡铂剂量前，通过每日肌酐和核医学肾小球滤过率（GFR）/肌酐清除率来评估肾功能。
在这 20 例患者的队列中，有 3 例因 GFR 下降而省略了卡铂剂量：1 例未发生肾毒性，1 例发生肾毒性但无需透析，1 例需要临时透析但恢复了肾功能。有 2 例患者 GFR 无变化，但发生了 HDC-ASCR 后肾衰竭，需要透析和 TRM。
在 HDC-ASCR 期间，每次给予卡铂前通过 GFR 评估肾功能，有助于保护接受高强度治疗的肿瘤/HSCT 患者的肾脏。尽管该研究的患者数量较少，这是该研究的主要局限性，但它表明存在严重的移植相关发病率和死亡率。因此，需要更大规模的研究来阐明卡铂剂量的最佳方法，以确保疗效和毒性之间的最佳平衡。
