Diffuse alveolar hemorrhage following gemtuzumab ozogamicin.
Diffuse alveolar hemorrhage following gemtuzumab ozogamicin.
复制标题
吉妥珠单抗奥佐米星后出现弥漫性肺泡出血。
DOI：
10.1038/sj.bmt.1704886
复制
发表时间：
2005
影响因子：
4.8
通讯作者：
Copelan,EA
中科院分区：
文献类型：
--
作者：
Lin,TS;Penza,SL;Avalos,BR;Lucarelli,MR;Farag,SS;Byrd,JC;Copelan,EA
Diffuse alveolar hemorrhage (DAH) or hemorrhagic alveolitis is a severe, often fatal, pulmonary complication of myeloablative stem cell transplantation (SCT). 1 The efficacy of current therapies for DAH remains unproven, although common practice is to treat patients with highdose, pulsed methylprednisolone. 2 The mortality of patients who require intubation and mechanical ventilation for DAH exceeds 80%. 3–5 While primarily a complication of myeloablative SCT in patients with hematologic malignancies, DAH has been described as a rare toxicity of nontransplant therapies. DAH has been observed after use of the antiglycoprotein IIb/IIIa receptor monoclonal antibody abciximab (ReoPro), 6, 7 but has not been associated with the humanized anti-CD33 monoclonal antibody gemtuzumab ozogamicin (Mylotarg). We report a case of DAH in a 51-year-old white male who received two doses of gemtuzumab ozogamicin for relapsed acute myelogenous leukemia (AML) after myeloablative allogeneic SCT. This patient initially achieved complete remission with 3+ 7 induction chemotherapy with daunorubicin and cytarabine, followed by one cycle of high-dose cytarabine. He relapsed 20 months after his initial diagnosis and received three cycles of mitoxantrone and VP-16, which failed to achieve remission. He underwent myeloablative allogeneic SCT from a matched unrelated donor. His preparative regimen consisted of busulfan 14 mg/kg, VP-16 60 mg/kg and cyclophosphamide 120mg/kg. He received methotrexate and cyclosporine as graft-versus-host-disease (GVHD) prophylaxis. Day+ 30 bone marrow biopsy showed remission, but day+ 162 bone marrow biopsy showed relapsed AML. He received gemtuzumab ozogamicin 9 mg/m2 26 weeks after his SCT. A similar dose was given 14 days later. At 3 days after his second dose, he developed cough, dyspnea and hypoxia, eventually requiring 60% oxygen by face mask. Serial chest radiographs showed development of bilateral, diffuse alveolar infiltrates, more pronounced in the upper lobes. Multiple sputum stains and cultures showed only altered oropharyngeal microbes, and DNA hybrid capture assays for cytomegalovirus were negative. Bronchoscopy 6 days after his day 15 dose showed heavy alveolar hemorrhage that worsened with bronchoalveolar lavage (BAL), numerous lymphocytes and alveolar macrophages with degenerative changes. Bacterial, acid fast, viral and fungal cultures from the BAL were all negative. He responded rapidly to methylprednisolone 1000mg daily, tapered 50% every 2–3 days. His symptoms improved rapidly, and he was discharged home without oxygen 12 days after initiation of high-dose steroid therapy. Bone marrow biopsy 30 days after his first dose of gemtuzumab ozogamicin showed persistent AML. He subsequently received high-dose cytarabine followed by two doses of donor lymphocyte infusion, but failed to respond to therapy. He died of AML 4.5 months after his first dose of gemtuzumab ozogamicin. Gemtuzumab ozogamicin is one of the few treatment options available to patients with AML who relapse after allogeneic SCT. However, gemtuzumab ozogamicin has significant toxicity, most notably hepatic veno-occlusive disease (VOD). 8, 9 DAH has not been described as a toxicity of gemtuzumab ozogamicin, although fatal hemorrhagic and pulmonary complications have been observed. In the initial phase II studies, three patients died of hemorrhage (two cerebral, one retroperitoneal), and three additional patients died of cerebral hemorrhage more than a month after receiving gemtuzumab ozogamicin. 8, 9 Eight patients developed acute pulmonary …
