Since the discovery of human leucocyte antigen (HLA) typing and its powerful impact on hematopoietic allogeneic bone marrow and stem cell transplantation (1), there has been much progress made with regards to the understanding between HLA antigen and HLA antibody including its role in successful graft function and prevention of graft versus host disease (GvHD) (2). The identification of donor specific HLA antibody (DSA) has been shown to predict graft failure (3, 4), making this knowledge more relevant in today’s age whereby there is increasing use of mismatched or haploidentical allogeneic hematopoietic stem cell transplantation. Various techniques have been established and constitute the desensitization protocols used prior to transplantation. These incorporate plasma exchange, rituximab, intravenous immunoglobulin and use of blood products to reduce or clear DSA (3). These strategies target a few pathways including depleting B cells, altering plasma cells, removing as well as modifying antibodies. We present a case whereby use of the anti-CD38 monoclonal antibody daratumumab (5) was able to successfully reduce DSA via its action of the cell surface glycoprotein highly expressed on plasma cells in a multiparous patient with early T-cell precursor acute lymphoblastic leukemia (ETP-ALL).

A 56 year old non-Caucasian female who was diagnosed with ETP-ALL developed complications of severe neutropenic sepsis after induction chemotherapy with fludarabine, cytarabine, granulocyte-colony stimulating factor and idarubicin (FLAG-Ida). She developed multiorgan dysfunction (MOD) and required care in the intensive care unit (ICU) for 11 days in view of respiratory failure, hemodynamic instability and acute kidney injury. Bone marrow assessment done on day 28 of treatment demonstrated measurable residual disease (MRD) negative status via flow cytometry. However, due to the infective complications sustained, she was severely deconditioned with critical illness myopathy and was bedbound with residual MOD.

Early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL) is a high-risk disease subtype of T-cell ALL with unique immunophenotypic and genomic features. It is characterized by the presence of CD7, absence of CD1a and CD8 and expression of one or more myeloid/stem cell markers (8, 9). Despite advancements in therapeutic strategies in ALL, ETP-ALL has been shown to have poor early treatment response to chemotherapy as well as significantly poorer long-term outcomes as compared to non-ETP-ALL patients (10, 11). In the search for identifying novel and effective treatment strategies in ETP-ALL, immunotherapy agents targeting its underlying molecular mechanisms have been sought (12–14). One such example is with the use of anti-CD38 monoclonal antibodies daratumumab and this has been supported by pre-clinical studies suggesting that CD38 is robustly expressed in T-ALL blasts thereby making it a potential effective target for daratumumab (15–17).

Along this same line, the use of anti-CD38 monoclonal antibodies have also been the agent of choice for tackling the important issue of DSA in transplantation (18, 19). The anti-CD38 monoclonal antibody exerts its therapeutic effect by targeting CD38, a cell surface glycoprotein highly expressed on plasma cells, thereby depleting antibody-producing plasma cells. Whilst there have been more experimental as well as clinical studies in evaluating daratumumab in kidney transplantation (20–23), its use has been shown to be effective in reducing DSA especially in cases whereby the standard of care desensitization protocols had been proven to be ineffective in reducing the MFI to less than moderate levels (24). Prior case reports in the use of daratumumab for desensitization of DSA were in patients with post essential thrombocythemia myelofibrosis, B-cell acute lymphoblastic leukemia, severe aplastic anemia and sickle cell disease (18, 24–26). Our case is the first reported patient with ETP-ALL to have shown the use of daratumumab in both controlling the underlying hematological disease process as well as reducing DSA levels effectively. In conclusion, daratumumab may be considered as a second line or salvage option for desensitization of DSA prior to haploidentical stem cell transplantation especially in multiparous ethnic-minority patients whom we often grapple with the issues of lack of donor availability and multiple DSA.