De Rosa Luca, Anghel Gabriel, Pandolfi Annino, Riccardi Massimo, Amodeo Rachele, Majolino Ignazio
Hematology and Bone Marrow Transplantation Unit, Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy.
Int J Hematol. 2004 Jan;79(1):85-91. doi: 10.1007/BF02983539.
Autografting with CD34+ cell-selected peripheral blood progenitor cells (PBPC) is often associated with a prolonged recovery time and a higher incidence of infections. The aim of our study was to evaluate whether underlying disease influences hemopoietic recovery and the infectious complications occurring after transplantation. We studied 19 breast cancer (BC) patients and 17 multiple myeloma (MM) patients entered in a high-dose chemotherapy (HDC) program of tandem autografting with CD34+ cell-selected PBPC. PBPC were collected after mobilizing chemotherapy plus granulocyte colony-stimulating factor and were processed for selection of CD34+ cells. After selection, a median of 53% CD34+ cells was recovered with a median final purity of 92% with no significant differences between the MM (52% and 92%, respectively) and BC (53% and 89%, respectively) patients. Medians of 4.5 x 10(6)/kg CD34+ cells (BC, 4.4 x 10(6)/kg; MM, 5.4 x 10(6)/kg) and 18 x 10(4)/kg colony-forming units-granulocyte-macrophage (BC, 21 x 10(4)/kg: MM, 16 x 10(4)/kg) were reinfused after each HDC. Twenty-six patients (10 MM and 16 BC) underwent tandem autografting, and 10 patients received only 1 autograft because of inadequate collection (5 patients), clinical condition (3 patients), and refusal (2 patients). In the BC patients, the HDC regimen included a high-dose melphalan course followed by an ICE (ifosfamide, carboplatin, and etoposide) course. In the MM patients, the regimen consisted of a course of high-dose melphalan therapy and a course of ICBV (idarubicin, cyclophosphamide [Cytoxan], BCNU, and etoposide) or total body irradiation, etoposide, and Cytoxan. We found a significantly prolonged time for neutrophil recovery to > 500/microL in the MM patients (13 days versus 10 days; P < .002), whereas the times for platelet recovery to > 20,000/microL in the two groups were not different (13 days versus 12 days; not significant). No late engraftment failures and no toxic deaths were observed. The incidences of extrahematologic toxicity were similar for the two patient groups. All patients received similar anti-infection prophylaxis for 3 months after transplantation. After 12 months of observation, we found a statistically significant higher incidence of bacterial infections in MM patients in both the early (77.8% versus 48.6%; P < .034) and the late (41.1% versus 0%; P < .014) posttransplantation periods, whereas the incidences of fungal infections were similar in the two groups. Viral infections consisted of herpes zoster virus infection in 2 patients of each group, and cytomegalovirus infection was observed in 3 MM patients and no BC patients. Our experience demonstrates a prolonged neutrophil recovery time and higher incidences of bacterial and viral infections in MM patients compared with BC patients. These observations, although limited by the small sample size, suggest that the underlying disease may influence the incidence of infections after CD34- cell-selected transplantation and should be considered in the planning of appropriate antimicrobial prophylaxis in the autologous transplantation setting.
用CD34+细胞分选的外周血祖细胞(PBPC)进行自体移植常伴有恢复时间延长和感染发生率较高的情况。我们研究的目的是评估基础疾病是否会影响造血恢复以及移植后发生的感染并发症。我们研究了19例乳腺癌(BC)患者和17例多发性骨髓瘤(MM)患者,这些患者进入了一个采用CD34+细胞分选的PBPC进行串联自体移植的大剂量化疗(HDC)方案。在动员化疗加粒细胞集落刺激因子后采集PBPC,并对其进行处理以分选CD34+细胞。分选后,MM患者(分别为52%和92%)和BC患者(分别为53%和89%)回收的CD34+细胞中位数为53%,最终纯度中位数为92%,两者之间无显著差异。每次HDC后回输的CD34+细胞中位数为4.5×10(6)/kg(BC患者为4.4×10(6)/kg;MM患者为5.4×10(6)/kg),集落形成单位 - 粒细胞 - 巨噬细胞的中位数为18×10(4)/kg(BC患者为21×10(4)/kg;MM患者为16×10(4)/kg)。26例患者(10例MM患者和16例BC患者)接受了串联自体移植,10例患者因采集不足(5例)、临床状况(3例)和拒绝(2例)仅接受了1次自体移植。在BC患者中,HDC方案包括一个大剂量美法仑疗程,随后是一个ICE(异环磷酰胺、卡铂和依托泊苷)疗程。在MM患者中,方案包括一个大剂量美法仑治疗疗程和一个ICBV(伊达比星、环磷酰胺[环磷酰胺]、卡莫司汀和依托泊苷)疗程或全身照射、依托泊苷和环磷酰胺疗程。我们发现MM患者中性粒细胞恢复至>500/μL的时间显著延长(13天对10天;P <.002),而两组血小板恢复至>20,000/μL的时间无差异(13天对12天;无显著性)。未观察到晚期植入失败和毒性死亡。两组患者血液学外毒性的发生率相似。所有患者在移植后3个月均接受了相似的抗感染预防措施。经过12个月的观察,我们发现MM患者在移植后早期(77.8%对48.6%;P <.034)和晚期(41.1%对0%;P <.014)细菌感染的发生率在统计学上显著更高,而两组真菌感染的发生率相似。病毒感染包括每组2例患者发生带状疱疹病毒感染,3例MM患者观察到巨细胞病毒感染,BC患者未观察到。我们的经验表明,与BC患者相比,MM患者中性粒细胞恢复时间延长,细菌和病毒感染的发生率更高。这些观察结果虽然受样本量小的限制,但表明基础疾病可能会影响CD34 - 细胞分选移植后感染的发生率,在自体移植环境中规划适当的抗菌预防措施时应予以考虑。