Lüke Florian, Harrer Dennis C, Hahn Joachim, Grube Matthias, Pukrop Tobias, Herr Wolfgang, Reichle Albrecht, Heudobler Daniel
Department of Internal Medicine III, Hematology and Oncology, University Hospital of Regensburg, Regensburg, Germany.
Front Pharmacol. 2021 Jun 2;12:599552. doi: 10.3389/fphar.2021.599552. eCollection 2021.
Spontaneous remission in acute lymphoblastic leukemia (ALL) is a rare phenomenon, which typically involves a pattern of feverish or septic disease followed by quick but mostly transient remission. We report on two male patients (46-year-old (pt. 1) and 19-year-old (pt. 2)) with CD20 positive, BCR-ABL negative common B-ALL. Patient 1 had received dexamethasone and cyclophosphamide (1.2 g) as a prephase therapy, followed by rituximab and a cumulative dose of 200 mg daunorubicin combined with 2 mg vincristine as an induction therapy. Patient 2 was treated with a reduced therapy regimen (Vincristine 1 mg, dexamethasone and 80 mg daunorubicin, 12-month mercaptopurine maintenance) due to (alcohol-related) toxic liver failure and pontine myelinolysis. Both patients developed severe septic disease just few days into induction treatment. Patient 1 suffered from pulmonary mycosis, which had to be resected eventually. Histological work-up revealed invasive mucor mycosis. Patient 2 presented with elevated serum aspergillus antigen and radiographic pulmonary lesions, indicative of pulmonary mycosis. In both patients, chemotherapy had to be interrupted and could not be resumed. Both patients recovered under broad antimicrobial, antifungal and prophylactic antiviral therapy and achieved molecular complete remission. At data cut-off remissions had been on-going for 34 months (pt. 1) and 8 years (pt. 2). Short-term, reduced intensity induction chemotherapy accompanied by severe fungal infections was followed by long-lasting continuous complete remissions in ALL. Thus, we hypothesize that infection-associated immunogenic responses may not only prevent early relapse of ALL but could also eradicate minimal residual disease. The effects of combined cytotoxic therapy and severe infection may also be mimicked by biomodulatory treatment strategies aiming at reorganizing pathologically altered cellular signaling networks. This could reduce toxicity and comorbidity in adult patients requiring leukemia treatment. Therefore, these two cases should encourage systematic studies on how leukemia stroma interaction can be harnessed to achieve long lasting control of ALL.
急性淋巴细胞白血病（ALL）的自发缓解是一种罕见现象，通常表现为发热或脓毒症，随后迅速但大多为短暂缓解。我们报告了两名男性患者（46岁（患者1）和19岁（患者2）），患有CD20阳性、BCR-ABL阴性的常见B-ALL。患者1在前期治疗中接受了地塞米松和环磷酰胺（1.2克），随后接受利妥昔单抗以及累积剂量为200毫克柔红霉素与2毫克长春新碱联合的诱导治疗。患者2因（酒精相关）中毒性肝衰竭和脑桥髓鞘溶解症接受了简化治疗方案（长春新碱1毫克、地塞米松和80毫克柔红霉素、12个月的巯嘌呤维持治疗）。两名患者在诱导治疗开始几天后均出现严重脓毒症。患者1患有肺真菌病，最终不得不进行切除。组织学检查显示为侵袭性毛霉菌病。患者2血清曲霉抗原升高且胸部X光显示肺部病变，提示肺真菌病。两名患者的化疗均不得不中断且无法恢复。两名患者在广泛的抗菌、抗真菌和预防性抗病毒治疗下康复并实现分子完全缓解。在数据截止时，缓解状态分别持续了34个月（患者1）和8年（患者2）。ALL患者在短期、低强度诱导化疗并伴有严重真菌感染后实现了长期持续完全缓解。因此，我们推测感染相关的免疫原性反应不仅可能预防ALL的早期复发，还可能根除微小残留病。旨在重组病理改变的细胞信号网络的生物调节治疗策略也可能模拟联合细胞毒性疗法和严重感染的效果。这可以降低需要白血病治疗的成年患者的毒性和合并症。因此，这两个病例应鼓励开展关于如何利用白血病与基质相互作用实现ALL长期控制的系统性研究。
