Pregnancy in Patents with CLL Systematic Review

Introduction: Chronic Lymphocytic Leukemia (CLL) is a hematologic malignancy characterized by the clonal expansion of non-functional, mature-appearing lymphocytes in the bone marrow, peripheral blood, and lymphoid tissues. While cases of CLL during pregnancy are rare,it is associated with many complications. It was reported that women with CLL are more susceptible to infections due to a weakened immune system; possibly leading to more complications. There is also increased risk of thrombocytopenia, which can increase the risk of bleeding during pregnancy and childbirth. This review aimed at identifying literature available on the complications in CLL and pregnancy as well as the data available on the potential therapeutic strategies.

Methods: A scoping review of case reports that discuss pregnant patients who were diagnosed with CLL were isolated. The effects of the disease on pregnancy outcomes regarding both mother and fetus were identified. Animal studies, reviews or non-original articles, and non-English articles were excluded from our study. FDA labels of medications in CLL were reviewed for data on pregnancy and animal outcomes. Information on those medications in pregnant patients were also identified where available.

Results: The search strategy across four databases yielded 448 articles. After eligibility assessment, 14 articles were included in the review. Cases were subdivided according to timing of pregnancy relative to CLL diagnosis (diagnosed before pregnancy or during pregnancy at early or late gestational periods). The pre-pregnancy reports were further subclassified based on the presence or absence of infection during pregnancy. None of the cases reported required immediate initiation of CLL therapy and only one case reported mortality post-delivery. This occurred in a patient with Richter transformation and no prior CLL treatments. There were no reported fetal malformations or severe adverse outcomes related to the infants in any of the reported pregnancies ( Figure 2). The included studies provided insights into various aspects of CLL during pregnancy, including patient demographics, diagnosis timing and methods, acquired infections, changes in white blood cell count, treatment approaches, pregnancy outcomes, and complications for both mother and fetus.

From the marketed pharmacological alternatives for CLL, most were not studied in pregnant humans with CLL ( Figure 1). However, venetoclax and rituximab have some data in pregnant patients with non-CLL indications. A case reported a pregnant refractory AML patient who received venetoclax with high dose cytarabine and mitoxantrone at 24 weeks of gestation. Bone marrow at 27 weeks showed complete remission and labor was induced at 28 weeks + 5 days after corticosteroid-induced lung maturation. The infant had hyperbilirubinemia, transient B-cell depletion and required ventilation. The baby recovered from all complications, although possible long-term effects are still unclear. The mother underwent allogeneic hematopoietic stem cell transplant.

In a 30-year-old female (pregnant at 28 weeks) with primary CNS lymphoma, weekly rituximab was given for 4 weeks with dexamethasone. After delivery through C-section at 31 weeks, the patient started definitive treatment with chemotherapy and autologous transplant. The infant required brief mechanical ventilation and had transient B-cell depletion at delivery until 4 months post-delivery. The baby required a course of post-exposure acyclovir despite not developing an infection. Both mother and baby survived with good outcomes at last follow-up (4 years post-delivery)

Conclusion: Despite the rarity of CLL occurrence during pregnancy, there is evident need of further studies and management guidelines in this population. This review provides insights into the possible pregnancy-related concerns in women with CLL at different disease stages. While watchful waiting is generally recommended due to CLL's slow progression, individual evaluation is crucial. If treatment is necessary, delaying therapy until the second or third trimesters may help mitigate the risk of fetal malformations. The increased susceptibility to infections resulting from the combined immunosuppressive effects of CLL and pregnancy should be carefully considered