ABSTRACT
Improved long-term survival rates after allogeneic hematopoietic cell transplantation (alloHCT) make family planning for young adult cancer survivors an important topic. However, treatment-related infertility risk poses challenges. To assess pregnancy and birth rates in a contemporary cohort, we conducted a national multicenter study using data from the German Transplant Registry, focusing on adult women aged 18-40 who underwent alloHCT between 2003 and 2018. Out of 2,654 transplanted women, 50 women experienced 74 pregnancies, occurring at a median of 4.7 years post-transplant. Fifty-seven of these resulted in live births (77%). The annual first birth rate among HCT recipients was 0.45% (95%CI: 0.31 - 0.59%), which is more than six times lower than in the general population. The probability of a live birth 10 years after HCT was 3.4 % (95%CI: 2.3- 4.5%). Factors associated with an increased likelihood of pregnancy were younger age at alloHCT, non-malignant transplant indications, no total-body-irradiation (TBI) or a cumulative dose of <8 Gray, and non-myeloablative/reduced-intensity conditioning. 72% of pregnancies occurred spontaneously, with assisted reproductive technologies (ART) used in the remaining cases. Preterm delivery and low birth weight were more common than in the general population. This study represents the largest dataset reporting pregnancies in a cohort of adult female alloHCT recipients. Our findings underscore a meaningful chance of pregnancy in alloHCT recipients. ART techniques are important and funding should be made available. However, the potential for spontaneous pregnancies should not be underestimated, and patients should be informed of the possibility of unexpected pregnancy despite reduced fertility. Further research is warranted to understand the impact of conditioning decisions on fertility preservation.
ABSTRACT
BACKGROUND: To date, in-depth analysis of leukapheresis products as starting material for CAR T-cell manufacturing, specifically Tisagenlecleucel production, are scarce. In this study, we report on lymphapheresis data for production of Tisagenlecleucel for elderly and pretreated lymphoma patients. STUDY DESIGN AND METHODS: Spectra Optia from Terumo BCT, Lakewood, CO, was employed for apheresis using the cMNC program. Apheresis success was defined as meeting a target total nucleated cell (TNC) count of ≥2 × 109 , a CD3-positive lymphocyte count of ≥1 × 109 and an overall viability of ≥70% in the lymphapheresis product. RESULTS: Twenty-three patients (age 37-77 years) and 24 apheresis runs were evaluated. The median CD3-positive lymphocyte count in peripheral blood at the beginning of apheresis was 565 cells/µl (range: 70-1345 cells/µl). Circulating lymphoma cells were detected in one patient prior to apheresis. Target criteria were met in 21 of 23 patients. The median TNC count in the apheresate was 11.2 × 109 (range: 2.9 × 109 -47.4 × 109 ). The median CD3-positive lymphocyte count in the apheresate was 2.55 × 109 (range: 0.370 × 109 -6.915 × 109 ), which resulted in a median collection efficiency for CD3-positive lymphocytes of 63.7% (range: 9.56%-93.6%). No adverse events associated with the apheresis process were observed. CONCLUSIONS: Lymphapheresis with the Spectra Optia cMNC program provided a sufficient quantity of CD3-positive lymphocytes for CAR T-cell manufacturing for the majority of patients despite their heavy pretreatment and advanced age. Moreover, we are the first to advocate early pre-emptive lymphocyte collection in DLBCL-NOS patients intended to undergo treatment with Tisagenlecleucel.
