TREATMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA DURING PREGNANCY ACCORDING TO THE ALL-2009 PROTOCOL

Introduction. Acute leukemias are very rarely diagnosed during pregnancy, which makes large prospective or comparative studies of treatment of leukemias during pregnancy difficult. In 2009, the Russian Acute Lymphoblastic Leukemia Study Group decided to include women diagnosed with acute lymphoblastic leukemia (ALL) during various stages of pregnancy into the ALL-2009 prospective clinical study to determine the predictive role of pregnancy at diagnosis, and to estimate efficacy and tolerance of the ALL-2009 protocol in pregnant women.

Materials and methods. During the period of 2009– 2017, 15  pregnant women with Ph-negative ALL aged 18–41 (median 28) years were enrolled in the multicenter clinical trial ALL-2009 (NCT number NCT01193933). Eleven women were treated at the National Research Center for Hematology in Moscow; the other four were treated in Russian regional hospitals. In cases when ALL was diagnosed during the first trimester of pregnancy (n = 3), the pregnancy was terminated. If ALL was diagnosed at week 34–40 (n = 3), the baby was delivered before the beginning of therapy. If ALL was diagnosed during the second or early third trimester, the treatment was performed during pregnancy. We compared toxicity and tolerance of chemotherapy according to the ALL-2009 protocol in pregnant patients and in young (30 years and younger) ALL patients. We also compared the results of treatment of pregnant patients with the control group (127 women of fertile age: 16–50 years old, with a median of 28 years old) enrolled in the study. For discussion of the results, we did a meta-analysis of available publications (retrieved via PubMed using the keywords “acute lymphoblastic leukemia” and “pregnancy”).

Results. There was a significantly higher frequency of T-cell ALL than of B-cell ALL (53.3% vs 46,7% compared to 26% vs 69,3% in the control group, p = 0.025). Other than that, there were no significant differences in clinical or laboratory data between the groups. No significant differences were found in the duration of neutropenia, or in the duration and frequency of breaks in chemotherapy compared with other patients below 30 enrolled in the study. However, during the first remission induction phase, pregnant patients required blood transfusions, specifically platelets, at a higher rate (77.8% vs 46.6% of cases). Results of the treatment were similar regardless of pregnancy at the time of diagnosis (86.7% of complete remissions, vs 85.8% in the control group). Differences in the frequency of refractory leukemia (13.3% vs 4.7%) were not statistically significant. There were no cases of early mortality. Long-term results were also similar, both in terms of overall survival (58.6% vs 43.3% in the control group) and in terms of disease-free survival (46% vs 51%). Relapse probability was the same (49% vs 40.3%). Overall, the pregnant patients gave birth to 12  children (6 boys and 6 girls) at weeks 34–38 (median 35 weeks) of pregnancy. At the time of writing, all children are healthy and are developing in accordance with their age, which ranges from 2 years 1 month to 8 years 10 months (median 5 years and 2 months).

Conclusion. The results of the study suggest that pregnancy at the time of diagnosis with ALL did not affect either the short-term or the long-term results of therapy according to the ALL-2009 protocol. The acceptable level of toxicity of the low-dose cytostatic therapy for both the mother and the child makes it possible to use the ALL-2009 protocol in treatment of pregnant patients.

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