Clinical Characteristics and Outcomes of Acute Lymphoblastic Leukemia in Adolescents and Young Adults in Malawi.
Clinical Characteristics and Outcomes of Acute Lymphoblastic Leukemia in Adolescents and Young Adults in Malawi.
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DOI：
10.1200/go.21.00388
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发表时间：
2022-06
影响因子：
4.5
通讯作者：
Painschab, Matthew S.
中科院分区：
文献类型：
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作者：
Kasonkanji, Edwards;Kimani, Stephen;Skiver, Brent;Ellis, Grace;Seguin, Ryan;Kaimila, Bongani;Tomoka, Tamiwe;Mulenga, Maurice;Montgomery, Nathan;Fedoriw, Yuri;Gopal, Satish;Westmorland, Katherine D.;Painschab, Matthew S.
关于撒哈拉以南非洲青少年和年轻人急性淋巴细胞性白血病(ALL)的治疗和结果的数据有限。我们描述了马拉维的一个前瞻性观察队列。马拉维Kamuzu中心医院从2013年到2019年登记了年龄在15-39岁之间的新诊断ALL患者；2020年12月对随访进行了审查。所有的诊断都是通过免疫组织化学和远程病理咨询现场确认的，这些咨询涉及马拉维和美国的病理学家。除4名患者外，其余患者均采用改良的儿科治疗方案(癌症和白血病B组10403方案)。关键的修改包括省略天冬酰胺酶和不增加甲氨蝶呤的剂量。在19名参与者中，年龄中位数为22岁(15-36岁)。在开始治疗的15名患者中，11名(73%)在诱导后缓解，1名(7%)在诱导期间死亡，2名(13%)患有顽固性疾病，1名(7%)潜逃。无一例患者失访。最终，11名确诊缓解的患者中有10人(91%)复发。首次缓解的中位持续时间为10(3-22)个月。在15名接受治疗的患者中，有12名(80%)在审查时已经死亡。在接受治疗的患者中，12个月和24个月的总生存率分别为50%(95%CI，23~72)和17%(95%CI，3~42)。中枢神经系统受累与较差的生存相关。有可能使用低成本、受儿科启发的疗法在低资源环境下治疗青少年和年轻人的ALL；然而，结果很差。支持性护理基础设施的成本和局限性都限制了诸如天冬酰胺酶等密集的细胞毒性方法。需要患者报告的结果才能了解生活质量和成本效益。至关重要的是，迫切需要创新的跨越式疗法，如单抗或双特异性抗体，以及适用于资源有限环境的可行的经济模式。
There are limited data on treatment and outcomes for acute lymphoblastic leukemia (ALL) among adolescents and young adults in sub-Saharan Africa. We describe a prospective observational cohort in Malawi. Patients age 15-39 years with newly diagnosed ALL at Kamuzu Central Hospital, Malawi, were enrolled from 2013 to 2019; follow-up was censored on December 2020. ALL diagnosis was confirmed on-site using immunohistochemistry and telepathology consultation involving pathologists in Malawi and the United States. All but four patients were treated with a modified pediatric-inspired regimen (Cancer and Leukemia Group B 10403 protocol). Key modifications included omission of asparaginase and no dose escalation for methotrexate. Of 19 participants, the median age was 22 (range 15-36) years. Of the 15 patients who initiated treatment, 11 (73%) achieved remission after induction, one (7%) died during induction, two (13%) had refractory disease, and one (7%) absconded. No patients were lost to follow-up. Eventually, 10 of 11 patients (91%) with confirmed remission relapsed. The median duration of first remission was 10 (range 3-22) months. Twelve of 15 treated patients (80%) had died at the time of censoring. Among treated patients, the 12- and 24-month overall survival was 50% (95% CI, 23 to 72) and 17% (95% CI, 3 to 42), respectively. CNS involvement was associated with worse survival. It is possible to treat adolescents and young adults with ALL in low-resource settings using a low-cost, pediatric-inspired regimen; however, outcomes are poor. Both cost and limitations in supportive care infrastructure limit intensive cytotoxic approaches such as asparaginase. Patient-reported outcomes are needed to understand the quality of life and cost-effectiveness. Critically, innovative, leap-frog therapies, such as monoclonal or bispecific antibodies, and feasible economic models for resource-limited settings are urgently needed.