Contributions
Type: Publication Only
Background
Acute lymphoblastic leukemia ALL accounts for about a third of acute leukemias diagnosed during pregnancy. Pregnancy is a common exclusion criteria for any clinical trial. RALL study group decided to include the pregnant women with ALL in the multicenter clinical trial ALL-2009 (ClinicalTrials.gov public site; NCT01193933). The protocol is based on non-intensive but non-interruptive treatment.
Aims
To evaluate efficacy and toxicity the ALL-2009 protocol for pregnant women with ALL.
Methods
From Jan 2009, till Dec 2014, 30 centers enrolled 263 Ph-negative ALL pts, among whom there were 13 pregnant women (3 - in 1st ; 3- in the 2nd and 7 - in 3rd trimester of pregnancy) from 3 hematological centers. The median age was 28 (18-32) years. B-cell ALL was diagnosed in 6 (46%) and T-cell ALL - 7 (54%) patients. 10 patients (77%) were attributed to a high-risk, 3 (23%) - to a standard risk group.
The treatment according the protocol ALL-2009 was carried out without deviations except the shift of L-asparaginase for later phases of treatment (after delivery) and applying intrathecal injections without methotrexate for those in whom chemotherapy was started during pregnancy.
Medical abortion was performed in 3 patients at the 1st trimester (10-11 weeks of gestation) during the prephase (7 days with prednisolone 60 mg/m2). 3 patients at 36-40 weeks of gestation were delivered before treatment and prephase was initiated after 2-3 days after delivery. All others (n=7) were started with chemotherapy during pregnancy (at 16, 19, 25, 28, 29, 31 and 34 weeks of gestation).
Results
All pregnant women were refractory to prednisolone defined by more than 25% of bone marrow blasts after 7 days of prephase. So dexamethasone was used for all further treatment. One patient is on the induction now, so CR rate was evaluated in 12. CR was achieved in 10 of 12 (83,3%), in 7 after the 1st phase and in 3 – after the 2nd induction phase. 2 patients had refractory ALL and died from the disease. There were no differences in the frequency of infections, duration of neutropenia, transfusion support during induction in comparison with common ALL pts.
In 3 pts of those who were treated during pregnancy delivery was carried out after the 1st induction phase, in 2 – during the 2nd phase, in 1 – after the 2nd phase. Gestational age at delivery was 34 weeks (33-39 weeks). At time of delivery 4 pts were and 2 were not in CR. One pregnant woman is still on the induction treatment. The median interval between the last administration of cytostatic drugs and delivery was 6 days (1-20 days). The median time from delivery to continuation of chemotherapy was 16 days (11-44 days). Chemotherapy duration during pregnancy constituted 5-9 weeks.
Totally 9 children were born at a median gestation time – 36 weeks (33-40). All are alive at a median 9 months (8-60 mo) and healthy.
Allo-HSCT was performed in 2 pts, auto-HSCT - 2. There were 2 relapses and 1 death in CR. The OS and DFS constituted 62% and 53% at 3 years, and these results did not differ from the other pts treated according ALL-2009 protocol (60% and 57%, respectively)
Summary
Our data demonstrate that ALL in pregnant women is characterized by higher frequency of T-cell phenotype and high risk disease, most cases occurred in the 2nd and 3rd trimester, CR rate is 83%. All born children are well. Long-term survival does not differ from that of the other patients on this protocol. So pregnancy should not be considered as an exclusion criteria for our protocol that is non-intensive, non-interruptive and easily reproducible.
Keyword(s): Acute lymphoblastic leukemia, Chemotherapy, Pregnancy
Type: Publication Only
Background
Acute lymphoblastic leukemia ALL accounts for about a third of acute leukemias diagnosed during pregnancy. Pregnancy is a common exclusion criteria for any clinical trial. RALL study group decided to include the pregnant women with ALL in the multicenter clinical trial ALL-2009 (ClinicalTrials.gov public site; NCT01193933). The protocol is based on non-intensive but non-interruptive treatment.
Aims
To evaluate efficacy and toxicity the ALL-2009 protocol for pregnant women with ALL.
Methods
From Jan 2009, till Dec 2014, 30 centers enrolled 263 Ph-negative ALL pts, among whom there were 13 pregnant women (3 - in 1st ; 3- in the 2nd and 7 - in 3rd trimester of pregnancy) from 3 hematological centers. The median age was 28 (18-32) years. B-cell ALL was diagnosed in 6 (46%) and T-cell ALL - 7 (54%) patients. 10 patients (77%) were attributed to a high-risk, 3 (23%) - to a standard risk group.
The treatment according the protocol ALL-2009 was carried out without deviations except the shift of L-asparaginase for later phases of treatment (after delivery) and applying intrathecal injections without methotrexate for those in whom chemotherapy was started during pregnancy.
Medical abortion was performed in 3 patients at the 1st trimester (10-11 weeks of gestation) during the prephase (7 days with prednisolone 60 mg/m2). 3 patients at 36-40 weeks of gestation were delivered before treatment and prephase was initiated after 2-3 days after delivery. All others (n=7) were started with chemotherapy during pregnancy (at 16, 19, 25, 28, 29, 31 and 34 weeks of gestation).
Results
All pregnant women were refractory to prednisolone defined by more than 25% of bone marrow blasts after 7 days of prephase. So dexamethasone was used for all further treatment. One patient is on the induction now, so CR rate was evaluated in 12. CR was achieved in 10 of 12 (83,3%), in 7 after the 1st phase and in 3 – after the 2nd induction phase. 2 patients had refractory ALL and died from the disease. There were no differences in the frequency of infections, duration of neutropenia, transfusion support during induction in comparison with common ALL pts.
In 3 pts of those who were treated during pregnancy delivery was carried out after the 1st induction phase, in 2 – during the 2nd phase, in 1 – after the 2nd phase. Gestational age at delivery was 34 weeks (33-39 weeks). At time of delivery 4 pts were and 2 were not in CR. One pregnant woman is still on the induction treatment. The median interval between the last administration of cytostatic drugs and delivery was 6 days (1-20 days). The median time from delivery to continuation of chemotherapy was 16 days (11-44 days). Chemotherapy duration during pregnancy constituted 5-9 weeks.
Totally 9 children were born at a median gestation time – 36 weeks (33-40). All are alive at a median 9 months (8-60 mo) and healthy.
Allo-HSCT was performed in 2 pts, auto-HSCT - 2. There were 2 relapses and 1 death in CR. The OS and DFS constituted 62% and 53% at 3 years, and these results did not differ from the other pts treated according ALL-2009 protocol (60% and 57%, respectively)
Summary
Our data demonstrate that ALL in pregnant women is characterized by higher frequency of T-cell phenotype and high risk disease, most cases occurred in the 2nd and 3rd trimester, CR rate is 83%. All born children are well. Long-term survival does not differ from that of the other patients on this protocol. So pregnancy should not be considered as an exclusion criteria for our protocol that is non-intensive, non-interruptive and easily reproducible.
Keyword(s): Acute lymphoblastic leukemia, Chemotherapy, Pregnancy