Immune Response As A Possible Mechanism Of Long-lasting Disease Control In Spontaneous Remission Of Mll/af9-positive Acute Myeloid Leukemia
Müller-Schmah, C., Solari, L., Weis, R., Pfeifer, D., Scheibenbogen, C., Trepel, M., May, A. M., Engelhardt, R., & Lübberight, M. (2012). Immune response as a possible mechanism of long-lasting disease control in spontaneous remission of MLL/AF9-positive acute myeloid leukemia. Annals of hematology, 91(1), 27–32. https://doi.org/10.1007/s00277-011-1332-y
View Original Source →Abstract
Spontaneous complete remission (CR) is a rare, poorly understood phenomenon in acute myeloid leukemia (AML). We describe the 10-year follow-up of a patient with MLL-AF9-positive AML (Müller et al. Eur J Haematol 73:62-66, 2004), including ex vivo antileukemic immune responses which may contribute to the long-lasting spontaneous CR (tantamount to cure). We could demonstrate strong in vitro cytotoxic activity mediated by the patient's serum (cryopreserved at diagnosis 2001) against myeloid cell lines. We also addressed cellular cytotoxic activity against myeloid leukemia cells. When the patient's natural killer (NK) cells (obtained in 2007) were tested against the K562 cell line, upregulation of CD107 occurred, implying that long-term CR in this patient could be due to NK cell-mediated disease control.
Case Details
Disease Location
Bone marrow
Personal Characteristics
61 -year-old male
Clinical Characteristics
March 2001, patient presented with headache, cough, exsiccosis, fever, leukocytopenia, anemia, and thrombocytopenia bone marrow exam revealed >90% blasts by cytology and histology diagnosis of acute myeloid leukemia (fab m5a) was made, with the translocation t(9;11)(q22;q23) as the only chromosomal abnormality patient had markedly reduced performance status (ecog4), and chemo was withheld IV antibiotics were started and patient's condition improved patient returned from a discharge with a relapse of the septic condition, recurrent leukopenia, and increase of ldh, but without blasts in peripheral blood. He was restarted on antibiotics which were altered due to a staphylococcus aureus from the indwelling venous catheter
Remission Characteristics
After IV antibiotics, clinical condition improved, and lab parameters normalized and a complete clearance of blasts from peripheral blood was observed patient was discharged after 13 days, but returned 11 days later after antibiotic change for staph and 17 days later, lab parameters including wbc and ldh returned to and remained normal follow ups monitored residual disease in the peripheral blood by right-pcr, and throughout extended follow up, right-pcr remained negative complete remission as noted by biopsy at day 96 nace staining showed massive hypercellularity and a dense infiltration with blasts at day 1 (>90%), and day 4(>80%). The biopsy taken at day 96 contained normocellular hematopoieses without evidence of an increased amount of blasts ihc of sequential biopsies also showed an increasing infiltration with CD3+ t lymphocytes in the first and second biopsy, while at remission, only expected, interstitial and nodular t lymphocytic infiltrates were observed. The marrow biopsy at 96 days contained only <1% apoptotic cells, when at day 1 (<5%) and day 2 (15% apoptotic)
Treatment & Mechanisms
Proposed Remission Mechanisms
Long-term disease control might be mediated bia expansion of specific t cell clones NK cells may be involved in the long-term antileukemic control (see article for more information on their study to test this) strong suggestion of contribution of a humoral antileukemic activity (e.g. Cytokine- or antibody-mediate) directed against the myeloid leukemic blasts sepsis is a possible mechanism for the activation of the immune system and clearance of leukemia, i.e. S. Aureus could have stimulated the release of tumor necrosis factor alpha, interleukin-1, interleukin-6, and interleukin-8, leading to an increase in NK and cytotoxic cells remission could be due to CD8 cells and humoral mechanisms, and long-term remission could be due to NK-mediated disease control
Clinical Treatment
IV antibiotic, ceftazidime and vancomycin IV antibiotics ceftazidime and vancomycin and then changed to imipenem/cilastatin for staph
Non-Clinical Treatment
None reported