We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Concomitant use of blinatumomab and donor lymphocyte infusion for mixed-phenotype acute leukemia: a case report with literature review

    Seren Durer

    Department of Medicine, Division of Hematology, Oncology, Blood & Marrow Transplantation, University of Arizona, Tucson, AZ 85724, USA

    ,
    Ceren Durer

    Department of Medicine, Division of Hematology, Oncology, Blood & Marrow Transplantation, University of Arizona, Tucson, AZ 85724, USA

    ,
    Madeeha Shafqat

    Department of Medicine, Division of Hematology, Oncology, Blood & Marrow Transplantation, University of Arizona, Tucson, AZ 85724, USA

    ,
    Isin Yagmur Comba

    Department of Medicine, University of Central Florida College of Medicine, Orlando, FL 32827, USA

    ,
    Saad Malik

    Department of Medicine, Division of Hematology, Oncology, Blood & Marrow Transplantation, University of Arizona, Tucson, AZ 85724, USA

    ,
    Warda Faridi

    Department of Medicine, Division of Hematology, Oncology, Blood & Marrow Transplantation, University of Arizona, Tucson, AZ 85724, USA

    ,
    Shehroz Aslam

    Department of Medicine, Division of Hematology, Oncology, Blood & Marrow Transplantation, University of Arizona, Tucson, AZ 85724, USA

    ,
    Awais Ijaz

    Department of Medicine, Division of Hematology, Oncology, Blood & Marrow Transplantation, University of Arizona, Tucson, AZ 85724, USA

    ,
    Muhammad Junaid Tariq

    Department of Medicine, Division of Hematology, Oncology, Blood & Marrow Transplantation, University of Arizona, Tucson, AZ 85724, USA

    ,
    Muhammad Asad Fraz

    Department of Medicine, Division of Hematology, Oncology, Blood & Marrow Transplantation, University of Arizona, Tucson, AZ 85724, USA

    ,
    Muhammad Usman

    Department of Medicine, Division of Hematology, Oncology, Blood & Marrow Transplantation, University of Arizona, Tucson, AZ 85724, USA

    ,
    Ali Y Khan

    Department of Medicine, Division of Hematology, Oncology, Blood & Marrow Transplantation, University of Arizona, Tucson, AZ 85724, USA

    ,
    Ali McBride

    Department of Pharmacy, University of Arizona Cancer Center, Tucson, AZ 85721, USA

    &
    Faiz Anwer

    *Author for correspondence:

    E-mail Address: anwerf@ccf.org

    Department of Hematology, Taussig Cancer Center, Medical Oncology, Cleveland Clinic, Cleveland, OH 44195, USA

    Published Online:https://doi.org/10.2217/imt-2018-0104

    Blinatumomab and donor lymphocyte infusion (DLI) combination is a promising cancer therapy, whereby blinatumomab might achieve an initial reduction in leukemic-cell burden using T cells, and after tumor clearance, DLI can potentially stimulate the donor immune system to achieve longer lasting remission. Here, we present a 51-year-old female with mixed phenotype acute leukemia who had a hematologic relapse 3 months after she received total body irradiation-based myeloablative allogeneic hematopoietic stem cell transplantation from an unrelated human leukocyte antigen matched (10/10) donor and achieved complete remission with minimal residual disease negativity by multi-parameter flow cytometry using the combination of blinatumomab and DLI. To the best of our knowledge, this is the first report to describe the use of blinatumomab and DLI combination therapy in the treatment of B/myeloid mixed phenotype acute leukemia.

    Papers of special note have been highlighted as: • of interest

    References

    • 1 Steensma DP. Oddballs: acute leukemias of mixed phenotype and ambiguous origin. Hematol. Oncol. Clin. N. Am. 25(6), 1235–1253 (2011).
    • 2 Wolach O, Stone RM. How I treat mixed-phenotype acute leukemia. Blood 125(16), 2477–2485 (2015).
    • 3 Matutes E, Pickl WF, Van't Veer M et al. Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 117(11), 3163–3171 (2011).
    • 4 Aribi A, Bueso-Ramos C, Estey E et al. Biphenotypic acute leukaemia: a case series. Br. J. Haematol. 138(2), 213–216 (2007).
    • 5 Yan L, Ping N, Zhu M et al. Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117 adult patients with mixed-phenotype acute leukemia defined by WHO-2008 classification. Haematologica 97(11), 1708–1712 (2012).
    • 6 Kim HJ. Mixed-phenotype acute leukemia (MPAL) and beyond. Blood Res. 51(4), 215–216 (2016).
    • 7 Weir EG, Ali Ansari-Lari M, Batista DA et al. Acute bilineal leukemia: a rare disease with poor outcome. Leukemia 21(11), 2264–2270 (2007).
    • 8 Van Den Ancker W, Westers TM, De Leeuw DC et al. A threshold of 10% for myeloperoxidase by flow cytometry is valid to classify acute leukemia of ambiguous and myeloid origin. Cytometry B Clin. Cytom. 84(2), 114–118 (2013).
    • 9 Arber DA, Orazi A, Hasserjian R et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20), 2391–2405 (2016).
    • 10 Charles NJ, Boyer DF. Mixed-phenotype acute leukemia: diagnostic criteria and pitfalls. Arch. Pathol. Lab. Med. 141(11), 1462–1468 (2017).
    • 11 Pomerantz A, Rodriguez-Rodriguez S, Demichelis-Gomez R et al. Mixed-phenotype acute leukemia: suboptimal treatment when the 2008/2016 WHO classification is used. Blood Res. 51(4), 233–241 (2016).
    • 12 Shimizu H, Saitoh T, Machida S et al. Allogeneic hematopoietic stem cell transplantation for adult patients with mixed phenotype acute leukemia: results of a matched-pair analysis. Eur. J. Haematol. 95(5), 455–460 (2015).
    • 13 Tian H, Xu Y, Liu L et al. Comparison of outcomes in mixed phenotype acute leukemia patients treated with chemotherapy and stem cell transplantation versus chemotherapy alone. Leuk. Res. 45, 40–46 (2016).
    • 14 Munker R, Labopin M, Esteve J, Schmid C, Mohty M, Nagler A. Mixed phenotype acute leukemia: outcomes with allogeneic stem cell transplantation. A retrospective study from the Acute Leukemia Working Party of the EBMT. Haematologica 102(12), 2134–2140 (2017).
    • 15 Getta BM, Roshal M, Zheng J et al. Allogeneic hematopoietic stem cell transplantation with myeloablative conditioning is associated with favorable outcomes in mixed phenotype acute leukemia. Biol. Blood Marrow Transplant. 23(11), 1879–1886 (2017).
    • 16 Hoffmann P, Hofmeister R, Brischwein K et al. Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-/CD3-bispecific single-chain antibody construct. Int. J. Cancer 115(1), 98–104 (2005).
    • 17 Topp MS, Gokbuget N, Zugmaier G et al. Phase II trial of the anti-CD19 bispecific T cell-engager blinatumomab shows hematologic and molecular remissions in patients with relapsed or refractory B-precursor acute lymphoblastic leukemia. J. Clin. Oncol. 32(36), 4134–4140 (2014).
    • 18 Ueda M, De Lima M, Caimi P et al. Concurrent blinatumomab and donor lymphocyte infusions for treatment of relapsed pre-B-cell ALL after allogeneic hematopoietic cell transplant. Bone Marrow Transplant. 51(9), 1253–1255 (2016). • This is the first report on the concurrent use of blinatumomab and donor lymphocyte infusion (DLI) in patients with relapsed B-acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation.
    • 19 Topp MS, Gökbuget N, Stein AS et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, Phase II study. Lancet Oncol. 16(1), 57–66 (2015). • This study has led to US FDA approval of blinatumomab for Ph-relapsed or refractory B-ALL. Complete remission (CR) was reported at 33% (63 of 189 patients), and CR with partial hematologic recovery (CRh) 10% (18 of 189 patients) after two cycles of therapy. Median relapse-free survival (RFS) was 5.9.
    • 20 Wolach O, Stone RM. Mixed-phenotype acute leukemia: current challenges in diagnosis and therapy. Curr. Opin. Hematol. 24(2), 139–145 (2017).
    • 21 Maruffi M, Sposto R, Oberley MJ, Kysh L, Orgel E. Therapy for children and adults with mixed phenotype acute leukemia: a systematic review and meta-analysis. Leukemia 32(7), 1515–1528 (2018).
    • 22 Kantarjian H, Stein A, Gokbuget N et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N. Engl. J. Med. 376(9), 836–847 (2017). • A Phase III TOWER study demonstrated a statistically significant difference in overall survival (OS) between blinatumomab (7.7 months) and chemotherapy arm (4 months). CR rate was 34 and 16% in the blinatumomab and chemotherapy group, respectively. MRD negativity status noted as 76% in the responders who achieved CR (full, partial or incomplete hematologic recovery) and 48% in the chemotherapy group.
    • 23 Gokbuget N, Dombret H, Bonifacio M et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood 131(14), 1522–1531 (2018).
    • 24 Collins RH Jr, Goldstein S, Giralt S et al. Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant. 26(5), 511–516 (2000).
    • 25 He F, Warlick E, Miller JS et al. Lymphodepleting chemotherapy with donor lymphocyte infusion post-allogeneic HCT for hematological malignancies is associated with severe, but therapy-responsive aGvHD. Bone Marrow Transplant. 51(8), 1107–1112 (2016).
    • 26 El Chaer F, Ali OM, Sausville EA et al. Treatment of CD19-positive mixed phenotype acute leukemia with blinatumomab. Am. J. Hematol. 94(1), E7–E8 (2019).
    • 27 Alcharakh M, Yun S, Dong Y et al. Blinatumomab-induced donor T-cell activation for post-stem cell transplant-relapsed acute CD19-positive biphenotypic leukemia. Immunotherapy 8(8), 847–852 (2016).
    • 28 Hamdi A, Mawad R, Bassett R et al. Central nervous system relapse in adults with acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation. Biol. Blood Marrow Transplant. 20(11), 1767–1771 (2014).
    • 29 Bondarenko SN, Maschan AA, Parovichnikova EN et al. The efficacy and toxicity of blinatumomab in patients with relapsed/refractory acute lymphoblastic leukemia: Russian multicenter experience. Blood 130(Suppl 1), 2604–2604 (2017).
    • 30 Linder K, Gandhiraj D, Hanmantgad M, Seiter K, Liu D. Complete remission after single agent blinatumomab in a patient with pre-B acute lymphoid leukemia relapsed and refractory to three prior regimens: hyperCVAD, high dose cytarabine mitoxantrone and CLAG. Exp. Hematol. Oncol. 5, 20 (2015).
    • 31 Khan MW, Gul Z. Blinatumomab may induce graft versus host leukemia in patients with pre-B ALL relapsing after hematopoietic stem cell transplant. Clin. Case Rep. 4(8), 743–746 (2016).
    • 32 Ronchetti AM, Leboeuf C, Raffoux E et al. Graft versus leukemia could participate of efficacy of blinatumomab in patients with B-lineage acute lymphoid leukemia relapsing after stem cell transplantation. J. Stem. Cell Res. Ther. 4(11), 251 (2014).
    • 33 Paul S, Regul L, Vollstadt O et al. Concurrent blinatumomab and donor lymphocytes for relapse of acute lymphoblastic leukemia after 2nd allogeneic transplantation-a case report. Bone Marrow Transplant. 52, S392–S393 (2017).