High early death rates, treatment resistance, and short survival of Black adolescents and young adults with AML.


Survival of patients with acute myeloid leukemia (AML) is inversely associated with age, but the impact of race on outcomes of adolescent and young adult (AYA; range, 18-39 years) patients is unknown. We compared survival of 89 non-Hispanic Black and 566 non-Hispanic White AYA patients with AML treated on frontline Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology protocols. Samples of 327 patients (50 Black and 277 White) were analyzed via targeted sequencing. Integrated genomic profiling was performed on select longitudinal samples. Black patients had worse outcomes, especially those aged 18 to 29 years, who had a higher early death rate (16% vs 3%; P=.002), lower complete remission rate (66% vs 83%; P=.01), and decreased overall survival (OS; 5-year rates: 22% vs 51%; P<.001) compared with White patients. Survival disparities persisted across cytogenetic groups: Black patients aged 18 to 29 years with non-core-binding factor (CBF)-AML had worse OS than White patients (5-year rates: 12% vs 44%; P<.001), including patients with cytogenetically normal AML (13% vs 50%; P<.003). Genetic features differed, including lower frequencies of normal karyotypes and NPM1 and biallelic CEBPA mutations, and higher frequencies of CBF rearrangements and ASXL1, BCOR, and KRAS mutations in Black patients. Integrated genomic analysis identified both known and novel somatic variants, and relative clonal stability at relapse. Reduced response rates to induction chemotherapy and leukemic clone persistence suggest a need for different treatment intensities and/or modalities in Black AYA patients with AML. Higher early death rates suggest a delay in diagnosis and treatment, calling for systematic changes to patient care.





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Publication Info

Larkin, Karilyn T, Deedra Nicolet, Benjamin J Kelly, Krzysztof Mrózek, Stephanie LaHaye, Katherine E Miller, Saranga Wijeratne, Gregory Wheeler, et al. (2022). High early death rates, treatment resistance, and short survival of Black adolescents and young adults with AML. Blood advances, 6(19). pp. 5570–5581. 10.1182/bloodadvances.2022007544 Retrieved from https://hdl.handle.net/10161/26963.

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Joseph Odell Moore

Professor Emeritus of Medicine

· Clinical research in the diagnosis and treatment of acute myeloid and lymphoid leukemias
· Malignant lymphoma
· Chronic myeloid and lymphoid leukemias
· Patient care and support programs and protocols
· Drug development and evaluation
· Soft tissue sarcoma
· Neuroendocrine tumors, carcinoid
· Delivery of continuing medical education
· Telemedicine
Research Program in Malignant Lymphoma and the Lymphocytic Leukemias (Acute and Chronic).

Duke has a long history of contribution to basic research and to clinical research programs which advance the understanding and treatment of the malignant lymphomas and the lymphocytic leukemias.
Currently, I am Duke principal investigator on a protocol for the investigation of Acute Lymphocytic Leukemia (CLL) designed to effect the first major change in induction therapy of this disease in the last twenty years. This is in cooperation with the overall PI at Memorial Sloan-Kettering Cancer Center. Additionally, we currently participate in a CALGB protocol for the primary treatment of Acute Lymphocytic Leukemia.

Chronic Lymphocytic Leukemia (CLL) represents a group of usually low-grade lymphoproliferative disorders. Duke's study of these disorders began with Dr. R. Wayne Rundles in the 1950s and 1960s, and proceeded on to current studies of both local initiative and participation and cooperative group protocols. Cancer and leukemic group B (CALGB) protocols currently investigate the use of rituximab and Fludarabine in CLL, and explore treatment with the investigative agent flavopiridol. Several other programs are currently being written in this cooperative group and will be participating in all of these. Additionally, we are currently extending the basic research and pharmacologic studies begun by Dr. Robert Silber (deceased) with The Clinical Pharmacology Section under the direction of Dr. Michael Colvin and his colleagues

Dr. Brice Weinberg has a long track record of innovative basic research in leukemias. He currently has initiated studies with several chemicals which inhibit nitric oxide (NO), a critical chemical transmitter in CLL and other cells. Initial pilot studies have demonstrated CLL cells are almost completely destroyed by inhibition of this enzyme. This work has the potential for bringing to the clinic an entirely new class
of chemical medications for the treatment of CLL.

In concert with the Duke Bone Marrow Transplant Program (DBMT), we are beginning to extend transplantation for Chronic Lymphocytic Leukemia to patients in all age groups, employing both standard allogeneic transplants, unrelated cord blood (UCBT) transplantation, and "mini-allo" transplants employing related donors. These studies are ongoing at this time and initial results are quite encouraging.

The Malignant Lymphomas represent an extremely varied group of diseases occurring in all age groups. These studies also encompass all of the cooperative efforts described above for CLL. We are currently participating in CALGB studies treating all levels of malignant lymphoma, and I am currently principal investigator (PI) on a program which is exploring the use of erythropoietin alpha (a growth factor stimulating the growth of red blood cells) in patients with malignant lymphomas and Hodgkin's disease. Likewise, I am principal investigator (PI) of another study using a white cell growth factor (SD-
to maintain white blood cell function in patients being treated with the aggressive program ESHAP, as a prelude to treatment with high dose chemotherapy and transplantation.

Dr. Jon P. Gockerman of our group is principal investigator employing the use of BEXXAR, a monoclonal antibody targeting CD20 and employed as a carrier for local radiation with I-131. These studies will facilitate the transfer of this particular very encouraging drug from the laboratory to general use in the clinic

Currently, Dr. Nelson Chao and his colleagues have developed, with our clinical help, a very comprehensive program for the transplantation of appropriate patients with malignant lymphoma, and with the malignant non-Hodgkin's lymphomas, and with Hodgkin's disease. Innovative programs are underway for treatment of mantle zone lymphoma and we are currently participating in a National Cancer Institute-generated study to treat intermediate grade malignant lymphoma with both chemotherapy and a unique immune treatment with anti-idiotypic antibody uniquely generated for each individual patient. Duke will be one of only three sites in the country responsible for this trial, but will also extend eligibility to other Duke cooperative sites under the Duke Oncology Consortium, of which I am the Medical Director.

In addition to the above transplantation studies, we are currently activating transplantation protocols employing allogeneic (sibling) donors, unrelated cord blood (UCB) donors, and matched unrelated donors (MUD).

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