Imatinib use during pregnancy and breast feeding: a case report and review of the literature.

INTRODUCTION: The development of imatinib as a therapeutic agent targeting BCR-ABL has increased the treatment options for chronic myeloid leukemia (CML) by significantly impacting outcomes, and imatinib is recommended by treatment guidelines as the first-line therapy. However, treatment of maternal CML with imatinib during gestation is not recommended because of the potential risk to the fetus. MATERIALS AND METHODS: We describe the clinical presentation, course and outcome of one pregnant patient with CML who was treated with imatinib. We review all pregnancies associated with imatinib documented in the literature. CASE PRESENTATION: A 27-year-old pregnant patient was diagnosed to have Philadelphia chromosome positive chronic phase CML in August 2007. Imatinib was administered (400 mg/day) between the 21st and 39th weeks of gestation. The patient tolerated the drug well and achieved complete hematological and cytogenetic remission. There were no imatinib-related maternal complications during the pregnancy. Fetal growth remained normal as well as amniotic fluid volume estimation. Labor was induced at the 39th gestational week, resulting in the uneventful vaginal delivery of a healthy male infant without any congenital anomaly. Umbilical cord blood and infant peripheral blood were collected at delivery. No postnatal complications occurred; however, imatinib was present in the umbilical cord blood (338 ng/mL) and in the infant's peripheral blood (478 ng/mL). Breast milk was collected on different postpartum days, and concentrations of imatinib were detected. At 10 months of age, the baby had normal growth and development. CONCLUSIONS: In light of reported cases and our experience, treatment of CML during the second and third trimesters of gestation and breast feeding seems to be safe, but the data are still limited and the effects of chronic exposure of infants to imatinib are not known. We think that each case should be examined and considered independently, and decisions should be individualized.

Meiotic segregation analysis of reciprocal translocations both in sperms and blastomeres.

Balanced chromosomal rearrangements could lead to unbalanced segregation gametes during meiosis. In this study, sperm flourescence in situ hybridization (FISH) analysis of meiotic segregation products of four reciprocal translocations; 46,XY,t(7;10)(q21;q22), 46,XY,t(15;17)(q11;p12), 46,XY,t(6;13)(p21.1;q32), and 46,XY,t(1;13)(q24;q10) are presented. In three out of these four cases with t(15;17), t(6;13), and t(1;13) additional blastomere FISH analyses are also provided. Multi-color FISH analysis was applied using diverse probe combinations specific for translocated chromosome segments. The average frequency of sperm nuclei bearing unbalanced products for t(7;10), t(15;17), t(6;13), and t(1;13) were 48.7%, 59.5%, 60.5%, and 62.9%, respectively. Frequencies of blastomeres comprising unbalanced products in cases with t(15;17), t(6;13), and t(1;13) were 80% (12 of 15), 60% (3 of 5), and 50% (2 of 4), respectively. Chi-square test analysis showed significant differences in the meiotic segregation patterns due to the distribution and numbers of the chiasmatas that could depend on the size of the translocated segments (P < 0.001). In conclusion, FISH analysis of sperm and blastomere for reciprocal translocation carriers effectively estimates the approximate risk of unbalanced products and this result might ensure valuable genetic counseling.

Pregnancy under treatment of imatinib and successful labor in a patient with chronic myelogenous leukemia (CML). Outcome of discontinuation of imatinib therapy after achieving a molecular remission.

Because of the teratogenicity data in rats, it is recommended that women treated with imatinib should be aware of the potential teratogenicity of imatinib and effective contraception should be used during imatinib therapy to prevent pregnancy. We describe successful pregnancy and delivery, without any congenital anomaly, in a patient with CML under treatment of imatinib. The fetus had been exposed to imatinib for 8 weeks. The patient remained off treatment during gestation and cytogenetic relapse of CML (5 months after discontinuation of imatinib therapy) developed at seventh month of gestation.

Successful pregnancy and delivery in a patient with chronic myelogenous leukemia (CML), and management of CML with leukapheresis during pregnancy: a case report and review of the literature.

Although infrequently seen, the management of cancer during pregnancy can be difficult for patients, their families and physicians. The concomitant occurrence of pregnancy and chronic myelogenous leukemia is uncommon. We describe the successful management of a 26-year-old woman in the first trimester of her pregnancy with chronic myelogenous leukemia (CML) in chronic phase by using only leukapheresis. She was treated with leukapheresis until her delivery at 36 weeks of gestation. The procedure was without significant adverse effects on the patient or fetus. We applied a total of 15 leukapheresis treatments throughout the pregnancy. The patient gave birth vaginally to a healthy 2800 g boy at 36 weeks of gestation. We conclude that leukapheresis may provide an alternative treatment to chemotherapy, alpha-interferon or imatinib in pregnant patients with CML, particularly with concern over their potential teratogenic and other adverse effects.

Frequency of recombinant and nonrecombinant products of pericentric inversion of chromosome 1 in sperm nuclei of carrier: by FISH technique.

Meiotic segregation products of carriers with pericentric inversion are very important for assessing the risk of unbalanced forms and appropriate genetic counseling. We investigated the incidence of recombinant and nonrecombinant products of chromosome 1 with pericentric inversion, in the sperm nuclei of the carrier by using triple color fluorescence in situ hybridization (FISH). The centromere specific and telomere specific probes for chromosome 1 were used. In the segregation analysis, 1,636 sperm nuclei were analyzed; 82.5% of the sperms were including normal or inverted chromosome 1, and the dup(p)/del(q) and del(p)/dup(q) recombinant products in sperm nuclei of our carrier were 8.7 and 7.3%, respectively. The number of recombinant products may be dependent on the formation of an inversion loop, which the number of the formation of chiasmata results in the different number of normal/balanced and recombinant products. The use of FISH, using different probe combination, in sperm nuclei has proved to be an accurate approach to determine the meiotic segregation patterns and could help to better establish a reproductive prognosis and genetic counseling.

Maternal and fetal outcomes in pregnancy complicated with acute leukemia: a single institutional experience with 10 pregnancies at 16 years.

The incidence of acute leukemia in pregnancy is low and the management of acute leukemia during pregnancy is difficult. We have observed a total of 10 pregnancies in 8 patients. Six of the patients had acute myeloblastic leukemia (AML) and two of them had acute lymphoblastic leukemia (ALL). Three of the pregnancies were diagnosed when the leukemia was in remission, six at the time of leukemia diagnosis and one at the time of leukemic relapse. Six of the pregnancies were found in first trimester, three in the second and one early in the third. Three pregnancies ended with spontaneous abortion, three with intrauterine death and three with medical termination. One of spontaneous abortions and one intrauterine death developed during combination chemotherapy (daunorubicin, cytarabine). Only 1 healthy baby survived from the 10 pregnancies and this child was the not exposed to chemotherapeutic agents. None of the cases had gynecologic and obstetric complications. Five of eight pregnant women with leukemia died because of the primary disease.

Plasma anti-oxidant status and lipid profile in non-gravida women with a history of pre-eclampsia.

OBJECTIVE: To investigate the total plasma anti-oxidant status, the plasma lipid profile and the uterine artery Doppler velocity waveform in formerly pre-eclamptic women. METHODS: Thirty-two formerly pre-eclamptic, non-gravida women constituted the study group, while 28 age-matched non-gravida women who had never had pre-eclampsia served as control subjects. On days 17-19 of their menstrual cycle, fasting plasma samples were collected for total anti-oxidant status (TAS) and lipid profile evaluation, and uterine artery Doppler velocity waveform studies were performed. Results were analyzed with Mann-Whitney U-test and Pearson correlation analysis. RESULTS: There was no significant difference between the groups in means of the uterine artery Doppler velocity waveforms and the plasma lipid levels, but body mass index values were significant (P < 0.005). The TAS value was subnormal in 72% of the formerly pre-eclamptic group and in 35% of the control group. The mean plasma TAS value was 1.20 +/- 0.05 mmol/L and was significantly lower in the study group when compared with the control group (P < 0.05). CONCLUSION: The current study reveals significantly decreased TAS in women with a history of pre-eclampsia, which may have an important role in pathophysiology.

Prenatal diagnosis of a fetus with pure partial trisomy 1q32-44 due to a familial balanced rearrangement.

We diagnosed a pure partial trisomy of the long arm of chromosome 1 in a fetus with multiple malformations detected prenatally. The father was a carrier of a balanced rearrangement involving 46,XY,inv(1)(qter-->p36::q32-->qter::p36-->q32). The fetus had preaxial polydactyly, low-set ears, macrocephaly, a prominent forehead, a broad and flat nasal bridge, a small mouth, an arched palate, micrognathia and unilateral renal agenesis. The couple had previously an infant with the same phenotypic abnormalities. The aberration was initially detected on amniocentesis with GTG banding and was confirmed by fluorescence in situ hybridization (FISH). Our case and other published pure trisomy 1q32-44 cases showed similarities, which allowed the further delineation of the trisomy 1q syndrome.