Fabbri Alberto, Cencini Emanuele, Alterini Renato, Rubegni Pietro, Rigacci Luigi, Delfino Chiara, Puccini Benedetta, Fimiani Michele, Bosi Alberto, Bocchia Monica, Pimpinelli Nicola
Division of Haematology, University Hospital of Siena, Siena, Italy.
Eur J Haematol. 2014 Aug;93(2):129-36. doi: 10.1111/ejh.12315. Epub 2014 Apr 4.
In primary cutaneous B-cell lymphomas (PCBCL), radiotherapy - or surgery in a minority of cases - is the first-line treatment in follicle center lymphoma (PCFCL) and marginal zone B-cell lymphoma (PCMZL). Conversely, patients with multifocal skin involvement or relapsed/refractory disease deserve a systemic chemotherapy. In diffuse large B-cell lymphoma, leg type (PCLBCL-LT), due its poorer outcome, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like regimens are the most commonly used frontline, although hard to propose in elderly patients. In this regard, the association of rituximab (R) and pegylated liposomal doxorubicin (PLD) can be considered a promising, alternative approach.
Based on the favorable results reported with R and PLD in several recent trials, we decided to test efficacy and safety of this combination.
Twelve patients with PCBCL were treated with R plus PLD, and 7 had relapsed disease. Treatment plan consisted of 2 monthly cycles of R 375 mg/m(2) and PLD 20 mg/m(2) day 1;15, followed (in responders) by two cycles given only at day 1. All patients received prophylactic pyridoxine to prevent palmar-plantar erythrodysesthesia (PPE).
Ten of 12 patients had a response (eight complete; two partial), remarkably 2/3 with PCLBCL-LT. Two patients did not respond (one progressive disease, PD, and one stable disease). Three patients died after a median follow-up of 56 months, two patients due to PD, and 1 due to a second neoplasm. Two out of 10 responders relapsed after 31 and 32 months, respectively. Hematological toxicity was negligible (one case of grade 2 neutropenia), as well as extra-hematological toxicity (two cases of grade 2 PPE).
These preliminary data suggest that R-PLD is effective and well tolerated in all subsets of PCBCL and may be offered frontline in indolent cases unsuitable for radiotherapy or surgery as well as in more aggressive cases with contraindications to CHOP-like regimens.
在原发性皮肤B细胞淋巴瘤(PCBCL)中,放疗(少数情况下为手术)是滤泡中心淋巴瘤(PCFCL)和边缘区B细胞淋巴瘤(PCMZL)的一线治疗方法。相反,有多灶性皮肤受累或复发/难治性疾病的患者需要进行全身化疗。在弥漫性大B细胞淋巴瘤腿部型(PCLBCL-LT)中,由于其预后较差,环磷酰胺、阿霉素、长春新碱和泼尼松(CHOP)样方案是最常用的一线治疗方案,尽管在老年患者中难以采用。在这方面,利妥昔单抗(R)和聚乙二醇化脂质体阿霉素(PLD)的联合应用可被视为一种有前景的替代方法。
基于最近几项试验中R和PLD报告的良好结果,我们决定测试这种联合治疗的疗效和安全性。
12例PCBCL患者接受R加PLD治疗,其中7例为复发疾病。治疗方案包括第1天和第15天每月2个周期的R 375mg/m²和PLD 20mg/m²;(对有反应者)随后仅在第1天给予2个周期。所有患者均接受预防性吡哆醇以预防手足红斑感觉异常(PPE)。
12例患者中有10例有反应(8例完全缓解;2例部分缓解),其中显著的是2/3为PCLBCL-LT。2例患者无反应(1例疾病进展,1例疾病稳定)。中位随访56个月后,3例患者死亡,2例死于疾病进展,1例死于第二种肿瘤。10例有反应者中有2例分别在31个月和32个月后复发。血液学毒性可忽略不计(1例2级中性粒细胞减少),血液外毒性也可忽略不计(2例2级PPE)。
这些初步数据表明,R-PLD在PCBCL的所有亚型中均有效且耐受性良好,可作为不适合放疗或手术的惰性病例以及对CHOP样方案有禁忌的侵袭性更强病例的一线治疗方案。