Welcome to Journal Club

Dr. Nahid Afroza

Phase B resident

Department of Haematology

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Background

Cancer is diagnosed in about 0.07% to 0.1% of pregnancies

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Second most common cause of maternal death

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Same cancer frequency and localization compared to non pregnant ones of the same age

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The incidence of leukemia during gestation is range from 1 in 75,000 to 100,000 pregnancies

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Cont…

• Acute myeloid Leukemia (AML) accounts for two-thirds of all cases

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• While acute lymphoid leukemia, chronic leukemia or myelodysplastic syndrome are rarely described

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Cont….

• Appropriate treatment significantly improved survival

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• Role of specific therapy during gestation has been emphasized while clinical experience accumulates

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• The therapeutic approaches to leukemia during pregnancy may be conditioned by several variables

Therapeutic approach depends on

Cont…

• 5 patients with AML, diagnosed during or immediately after pregnancy, were identified in the institutional database

• AML diagnosis was performed according to World Health Organization (WHO)

Children outcomes�

Children outcomes

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• In the described population, one case of AML diagnosed concomitantly with intrauterine fetal death

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• One asked for a therapeutic abortion before starting chemotherapy

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• Three remaining patients continued a regular pregnancy and delivered healthy baby

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• Only one child exposed to chemotherapy during the gestational period

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Cont….

• The newborn needed oxygen therapy immediately after birth

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• Suffered of mild leukopenia,resolved spontaneously after a few days

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• He is 5 years old and showed

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-Normal neurodevelopment

-No impairments to general health and growth

-Normal cardiac outcome by echocardiography. howed

Cont….

• Other two children born by a cesarean delivery at diagnosis

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• Before the start of a chemotherapy

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• Follow up were normal at birth, 1 and 5 years old, respectively.

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Discussion….

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• Clinical picture of AML overlap of some common symptoms reported during pregnancy

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• Might delay the diagnostic and appropriate therapy

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Symptoms

Differential diagnosis

Investigations for correct differentials

Presentation of AML

Cont….

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• Thrombosis could affect placental vessels, impairing fetal growth and survival

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• Intrauterine death may be the result of hypoxia caused by placental ischaemic infarction and leukemic infiltration

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Cont….

• When leukemia is suspected, Marrow samples should be obtained for
• Morphological
• Immunophenotypic
• Cytogenetic and molecular analyses

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• To allow accurate sub-typing and correct prognostication
• AML associated to pregnancy is rare and only small patients series have been reported

Cont…

• The ant leukemic therapies during pregnancy may differ from gold standards , conditioned by several variables

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• Including-

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Fetal death during chemotherapy

Fetal toxicities are

Cont….

• Patients diagnosed during first trimester underwent abortion

• Treated with induction chemotherapy

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• Few cases treated with chemotherapy during first trimester

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• Poor pregnancy outcomes reported with congenital anomalies and spontaneous abortions

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• Prolonged delay in therapy associated with worse maternal outcome

Cont….

• A multidisciplinary team created to coordinate all the diagnostic and therapeutic steps

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• Including the :
• Planning of a cesarean delivery before or between courses of chemotherapy

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- After maternal bone-marrow reconstitution, to avoid maternal and neonatal pancytopenia.

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Cont….

• To minimize risks for mother and fetus, a near term cesarean delivery (>35–37 weeks) remains the main goal

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• Survival following delivery at or beyond 28 weeks gestation are >90%

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• Even higher (>95%) at or beyond 32 weeks gestation

Cont….

• A cesarean section should be planned before chemotherapy

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• Or at peripheral blood counts recovery after the treatment cycle

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• Chemotherapy should not be administered after 35th gestational week

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Cont….

• Ultrasound to document fetal growth , development, cardiac function and placental status, as well as tocographic assessment

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• Delivery at an earlier gestational age , a pharmacologic enhancement of fetal lung maturation by corticosteroids

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• Breast feeding is contraindicated during maternal anti-leukemic program

Cont….

• Use of hydroxycarbamide before starting induction chemotherapy should be avoided

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• Except in cases of hyperleukocytosis (WBC greater then 100 × 109/L)

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• An alternative is leukapheresis

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• Allows rapid reduction of WBC counts in symptomatic patients.

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Monitoring

Cont….

• Continuous-flow cell separators used to ensure the lowest extracorporeal volume

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• Saline or 5% human albumin used as replacement fluid

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• Fresh frozen plasma used in case of coagulation factors deficiencies or intravascular coagulation .

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Cont….

• A single chemotherapy cycle with daunorubicin and cytarabine is recommended for induction

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• Daunorubicin 60 mg/m2 on days 1–3 and cytarabine 100 mg/m2 continuous infusion on days 1–7

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• Standard consolidation therapy with intermediate or high dose cytarabine is preferred

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Cont…

• Idarubicin, has an increased placental transfer and higher potential foetal toxicity,

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• Daunorubicin remains the anthracycline of choice

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• It is highly advisable to monitor -
• Fetal cardiac function for anthracycline
• Limb morphogenesis for teratogenic potential of cytarabine (10%)

Cont….

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• Acute promyelocytic leukemia (APL) represents a special situation

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• Usually associated with coagulopathy

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• Platelet transfusions should be considered to maintain a platelet count of more than 30 × 109/L

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• Fresh frozen plasma for a fibrinogen level higher than 150 mg/dl.

Cont….

• Management during the first trimester of pregnancy separated from the second/third trimester

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• All-trans retinoic acid (ATRA) is the cornerstone of APL treatment

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• It can be potential teratogenic

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• Should be avoided during the first trimester

Cont….

• Arsenic trioxide has a high potential embryotoxicity

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• Cannot be recommend at any stage of pregnancy

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• Anthracycline alone is recommended during the first trimester

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• Treatment by ATRA alone during the second and the third trimester until complete remission can be proposed

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Supportive therapies during pregnancy

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• First line antiemetic agent are antihistamines
• Cyclizine
• Promethazine
• Ondansetron could be administered safely during first trimester

Cont….

• Metoclopromide may induce maternal dystonic reactions, therefore considered as a second line drug.

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• Use of granulocyte colony stimulating factor during gestation was rarely reported

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• But available data suggest its safe use in the second and third trimesters

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Cont….

• Penicillins were not associated to injurious fetal effects

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• Except the combination of amoxicillin and clavulonate

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• Aminoglycosides, quinolones , sulphonamides and tetracyclines are not permitted

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• While the main systemic antifungal drug safely used was amphotericin B or lipid derivates

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Cont….

• Cytomegalovirus negative blood products are first choice

• The prognosis is worse only when appropriate treatment is significantly delayed

Cont….

• In this series, induction treatment consisted of a combination of anthracyclines and cytarabine

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• The only patient treated before delivery received standard dosage of cytarabine and daunorubicin at a reduced dosage of 40 mg/m2 (days 1,2,3)

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Conclusions….

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• The cases represented a clinical challenge

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• The cases diagnosed in advanced gestational age, postponed the leukemia treatment after delivery

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• The case occurring in the first trimester, asked for therapeutic abortion.

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Cont….

• If chemotherapy is administered during pregnancy, extensive and continuous monitoring of fetal cardiac function and congenital malformation is mandatory

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• Cord blood stem cells should be collected and stored in the event that an irreversible bone marrow failure syndrome should develop in the fetus.

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