Abstract
An older chronologic age has been a consistent predictor of poor outcomes in hematopoietic stem cell transplantation (HSCT), mainly due to non-relapse mortality (NRM). Therefore, non-curative treatment strategies are commonly adopted for these patients. However, mortality and treatment toxicity has decreased as a result of improved supportive measures, such as reduced intensity conditioning regimens and optimized infection management. T-cell replete haploidentical HSCT emerged as a feasible alternative for leukemia patients without substantial differences in outcomes when compared to fully matched related donor. We report an old adult woman treated with haploidentical HSCT.
A 78 year-old female patient presented with anemia, leukocytosis, thrombocytopenia and blasts in the peripheral blood. Diagnosis of acute myelogenous leukemia was established. Conventional cytogenetic demonstrated chromosome eight trisomy, and FISH was negative for other common MDS/AML cytogenetic abnormalities. FLT3-ITD and NPM1 mutations were negative. Her medical history was negative except for heavy smoking. Considering the patients advanced age, the first attending physician chose not to administer intensive treatment and started on decitabine 20 mg/m2 for 5 days. She was refractory to the first-line treatment with persistent cytopenias and blasts in the peripheral blood four weeks after treatment was started. Comprehensive geriatric assessment was performed. She was considered independent for Basic Activities of Daily Living (ADL score 6) and Instrumental Activities of Daily Living (IADL score 27), without cognitive impairment in mini-mental state examination (MMSE score 30), at risk of malnutrition in mini nutritional assessment (MNA 9). As she was considered fit, we decided to perform high-dose chemotherapy with idarubicin and cytarabine, but, once more, the disease was refractory. A rescue regimen was attempted with high-dose cytarabine and mitoxantrone, again, with no response. After discussing pros and cons with the patient and the family, we decided to start Another regimen consisting of topotecan and high dose cytarabine immediately followed by allogeneic hematopoietic stem cell transplantation (HSCT). At day 14, she had 3% blasts in the BM aspirate a T-cell replete haploidentical HSCT using her 52 year-old son as donor and mobilized peripheral blood as stem cell source was performed. Conditioning regimen consisted of fludarabine, cyclophosphamide, TBI 2Gy and post-transplant cyclophosphamide. Graft versus host disease (GVHD) prophylaxis consisted of mycophenolate mofetil and cyclosporine. She had neutrophil engraftment with complete donor chimerism at day+15 and platelet engraftment at day+17. At day+48, she had mild (stage II) skin acute GVHD resolved with topical steroids. Cyclosporine was withdrawn at day+ 93. Due to high relapse risk, the patient was started on monthly post-transplant azacitidine 36 mg/m2. At day+100 the patient remained in complete remission, complete donor chimerism in peripheral blood and bone marrow. Functionality was preserved (ADL score 6 and IADL score 24), presented discrete cognitive impairment (MMSE 28) and malnoutrition (MNA 5). She is now at day+182, doing well and performing again all usual daily activities.
To the best of our knowledge, this is the oldest patient treated with haploidentical HSCT. Post transplant cyclophosphamide as T cell depletion strategy in haploidentical HSCT is well tolerated and widely available, being therefore an excellent alternative for patients without conventional donors who require immediate transplant. Older adults with hematologic malignancies are a heterogeneous group and decisions based on chronological age alone are clearly inappropriate. Recently, geriatric assessment proved to be an important prognostic tool in acute leukemia and may be useful in HSCT. In experienced centers, haploidentical HSCT in older adults may be a safe procedure and more accurate pre-transplantation risk stratification tools should be developed.
Timeline of main events during hematopoietic stem cell transplant.
No relevant conflicts of interest to declare.
