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Acta Haematol 1990;83:140-144
Acute Leukemia during Pregnancy
Association with Immune-Mediated Thrombocytopenia in Mother and Infant Hisashi Gondo, Yasuo Hamasaki, Hideki Nakayama, Tsutomu Kondo, Johji Mitsuuchi, Yasuko Kawaga, Shuichi Taniguchi, Mine Hatada, Yoshiyuki Niho
Division of Internal Medicine, Sanshinkai Hara Hospital; Fukuoka Municipal Children Hospital Medical Center; Fukuoka Red Cross Blood Center, and First Department of Internal Medicine, Kyushu University, Fukuoka, Japan
Key Words. Acute myelogenous leukemia • Blood group change • Immune-mediated thrombocytopenia • Passive immune thrombocytopenia • Pregnancy Abstract. A 29-year-old female in the 20th week of pregnancy was admitted because of a change in the ABO blood group and bleeding tendency. Acute myelogenous leukemia was diagnosed with a weak reaction of red blood cells with anti-A antibody and a decreased level of A-transferase activity. Though the patient tolerated intensive chemotherapy and achieved complete remission, thrombocytopenia persisted after consolidation chemotherapy. Since platelet-associated IgG was elevated, thrombocytopenia was considered to be immunemediated. In the third trimester, premature separation of the normally implanted placenta developed and cesarean section was performed. The male baby was also thrombocytopenic, but successfully treated with y-globulin.
Acute leukemia is among the most common malig nancies in women of the reproductive age. However, its incidence during pregnancy is still low and is esti mated to be similar to that of acute leukemia in the general female population [1], Experience in the treat ment of acute leukemia during pregnancy is limited. Immune thrombocytopenic purpura (ITP) also fre quently occurs in young women. Approximately half the infants of mothers with autoimmune thrombocy topenia are reported to be thrombocytopenic [2], Mo ther and fetus are sometimes at risk of serious throm bocytopenia during pregnancy. Careful management is required to prevent fatal bleeding under this situa tion [3]. This report describes a woman with acute myeloge nous leukemia (AML) associated with immune-medi ated thrombocytopenia during pregnancy. The fetus was saved by cesarean section in emergency when premature separation of the normally implanted pla centa developed in the third trimester. The infant was also thrombocytopenic but successfully treated with high-dose y-globulin.
Case Report A 29-year-old pregnant female was referred to us for the evalua tion of an ABO blood group change from AB to B and bleeding tendency. Physical examination revealed petechiae, ecchymosis, and purpura, but neither hepatosplenomegaly nor lymphadenopathy. On admission, a WBC count was 19.3 x 19Vl with 61 % blastic cells. Hemoglobin concentration and platelet count were 10.8 g/dl and 8 x lO’/l, respectively. Bone marrow aspiration showed hypercellularity with a marked increase in blastic cells (52.8%), which were positive for myeloperoxidase staining. Surface marker analy sis using monoclonal antibodies indicated that blastic cells ex pressed CD13 and CD33 antigens, which were compatible with the myeloid lineage. Based upon these findings, the diagnosis of AML (FAB classification, M2) was made. Cytogenetic analysis gave no chromosomal abnormalities. Coagulation tests were normal. Serum lactate dehydrogenase was slightly elevated, but liver and renal function tests were normal. Rheumatoid factor, antinuclear antibody and microsome test were positive while immune complex was not detected. ABO blood group analysis revealed that the red cells weakly agglutinated with anti-A antibody and the serum level of a-(l —3)N-acetylgalactosaminyltransferase (A-transferase) ac tivity was decreased (table 1). However, these changes disappeared during complete remission. On admission, the patient was in the 20th week of gestation. She was treated with combination chemotherapy for remission induc tion, consisting of N(4)-behenoyl-l-p-D-arabinofuranosylcytosine (BHAC, 170 mg/m2 for 10 days), mitoxantrone (MIT, 6 mg/m2 for
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Introduction
141
AML during Pregnancy Associated with ITP Table 1. Results of ABO blood group typing Reaction with antibodies or cells
Serum transferase activity1
anti-A
anti-B
anti-H
A| cells
B cells
O cells
A (control)
B (control)2
On admission (June 17, 1988)
+W
4+
4+
-
-
-
1:8(1:32)
1:32(1:32)
During remission (Nov. 14, 1988)
4+
4+
2+
-
-
-
1:32(1:32)
NT
W = Weakly agglutinated; NT = not tested. 1 A-transferase = cx-(l —3)N-acetylgalactosaminyltransferase; B-transferase: a-(l —3)galactosyl-transferase. 2 The serum from normal AB blood group was used for control.
20 June
30
10
20 July
30
10
20 Aug
3D
10
20 Sep
30
10 Oct
5 days), 6-mercaptopurine (6-MP, 70 mg/m2for 10 days), and pred nisolone (PSL, 20 mg/m2 for 10 days with tapering) as shown in figure 1. Complete remission was confirmed with bone marrow aspiration 1 month after remission induction chemotherapy. Subse quently she received the same regimen as during consolidation of the complete remission. Despite continuing complete remission, thrombocytopenia persisted thereafter and platelet-associated IgG (PAIgG) was found to be markedly increased. However, platelet counts gradually increased and the level of PAIgG decreased in re sponse to the treatment with PSL (fig. 1). At the beginning of the third trimester, uterine contractions began, but could be controlled by administering ritodrine. We in itially planned vaginal delivery in the 35th week of gestation. On October 1, 1988 (35 weeks and 4 days of gestation), however, mas sive genital bleeding suddenly occurred. The diagnosis of prema ture separation of the normally implanted placenta was made and cesarean section was performed in emergency. The male baby had low birth weight (1,882 g) and was found to be thrombo cytopenic and leukocytopenic (fig. 2). This thrombocytopenia Fig. 2. Clinical course of the infant after birth, r-gl = ywas successfully treated with high-dose y-globulin (400 mg/kg/day Globulin.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 10:25:41 AM
Fig. 1. Clinical course of the patient. Plate let-associated IgG (PAIgG) is expressed by PLT ng/10xl056 platelets (normal
Acta Haematol 1990;83:140-144
Acute Leukemia during Pregnancy
Association with Immune-Mediated Thrombocytopenia in Mother and Infant Hisashi Gondo, Yasuo Hamasaki, Hideki Nakayama, Tsutomu Kondo, Johji Mitsuuchi, Yasuko Kawaga, Shuichi Taniguchi, Mine Hatada, Yoshiyuki Niho
Division of Internal Medicine, Sanshinkai Hara Hospital; Fukuoka Municipal Children Hospital Medical Center; Fukuoka Red Cross Blood Center, and First Department of Internal Medicine, Kyushu University, Fukuoka, Japan
Key Words. Acute myelogenous leukemia • Blood group change • Immune-mediated thrombocytopenia • Passive immune thrombocytopenia • Pregnancy Abstract. A 29-year-old female in the 20th week of pregnancy was admitted because of a change in the ABO blood group and bleeding tendency. Acute myelogenous leukemia was diagnosed with a weak reaction of red blood cells with anti-A antibody and a decreased level of A-transferase activity. Though the patient tolerated intensive chemotherapy and achieved complete remission, thrombocytopenia persisted after consolidation chemotherapy. Since platelet-associated IgG was elevated, thrombocytopenia was considered to be immunemediated. In the third trimester, premature separation of the normally implanted placenta developed and cesarean section was performed. The male baby was also thrombocytopenic, but successfully treated with y-globulin.
Acute leukemia is among the most common malig nancies in women of the reproductive age. However, its incidence during pregnancy is still low and is esti mated to be similar to that of acute leukemia in the general female population [1], Experience in the treat ment of acute leukemia during pregnancy is limited. Immune thrombocytopenic purpura (ITP) also fre quently occurs in young women. Approximately half the infants of mothers with autoimmune thrombocy topenia are reported to be thrombocytopenic [2], Mo ther and fetus are sometimes at risk of serious throm bocytopenia during pregnancy. Careful management is required to prevent fatal bleeding under this situa tion [3]. This report describes a woman with acute myeloge nous leukemia (AML) associated with immune-medi ated thrombocytopenia during pregnancy. The fetus was saved by cesarean section in emergency when premature separation of the normally implanted pla centa developed in the third trimester. The infant was also thrombocytopenic but successfully treated with high-dose y-globulin.
Case Report A 29-year-old pregnant female was referred to us for the evalua tion of an ABO blood group change from AB to B and bleeding tendency. Physical examination revealed petechiae, ecchymosis, and purpura, but neither hepatosplenomegaly nor lymphadenopathy. On admission, a WBC count was 19.3 x 19Vl with 61 % blastic cells. Hemoglobin concentration and platelet count were 10.8 g/dl and 8 x lO’/l, respectively. Bone marrow aspiration showed hypercellularity with a marked increase in blastic cells (52.8%), which were positive for myeloperoxidase staining. Surface marker analy sis using monoclonal antibodies indicated that blastic cells ex pressed CD13 and CD33 antigens, which were compatible with the myeloid lineage. Based upon these findings, the diagnosis of AML (FAB classification, M2) was made. Cytogenetic analysis gave no chromosomal abnormalities. Coagulation tests were normal. Serum lactate dehydrogenase was slightly elevated, but liver and renal function tests were normal. Rheumatoid factor, antinuclear antibody and microsome test were positive while immune complex was not detected. ABO blood group analysis revealed that the red cells weakly agglutinated with anti-A antibody and the serum level of a-(l —3)N-acetylgalactosaminyltransferase (A-transferase) ac tivity was decreased (table 1). However, these changes disappeared during complete remission. On admission, the patient was in the 20th week of gestation. She was treated with combination chemotherapy for remission induc tion, consisting of N(4)-behenoyl-l-p-D-arabinofuranosylcytosine (BHAC, 170 mg/m2 for 10 days), mitoxantrone (MIT, 6 mg/m2 for
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 10:25:41 AM
Introduction
141
AML during Pregnancy Associated with ITP Table 1. Results of ABO blood group typing Reaction with antibodies or cells
Serum transferase activity1
anti-A
anti-B
anti-H
A| cells
B cells
O cells
A (control)
B (control)2
On admission (June 17, 1988)
+W
4+
4+
-
-
-
1:8(1:32)
1:32(1:32)
During remission (Nov. 14, 1988)
4+
4+
2+
-
-
-
1:32(1:32)
NT
W = Weakly agglutinated; NT = not tested. 1 A-transferase = cx-(l —3)N-acetylgalactosaminyltransferase; B-transferase: a-(l —3)galactosyl-transferase. 2 The serum from normal AB blood group was used for control.
20 June
30
10
20 July
30
10
20 Aug
3D
10
20 Sep
30
10 Oct
5 days), 6-mercaptopurine (6-MP, 70 mg/m2for 10 days), and pred nisolone (PSL, 20 mg/m2 for 10 days with tapering) as shown in figure 1. Complete remission was confirmed with bone marrow aspiration 1 month after remission induction chemotherapy. Subse quently she received the same regimen as during consolidation of the complete remission. Despite continuing complete remission, thrombocytopenia persisted thereafter and platelet-associated IgG (PAIgG) was found to be markedly increased. However, platelet counts gradually increased and the level of PAIgG decreased in re sponse to the treatment with PSL (fig. 1). At the beginning of the third trimester, uterine contractions began, but could be controlled by administering ritodrine. We in itially planned vaginal delivery in the 35th week of gestation. On October 1, 1988 (35 weeks and 4 days of gestation), however, mas sive genital bleeding suddenly occurred. The diagnosis of prema ture separation of the normally implanted placenta was made and cesarean section was performed in emergency. The male baby had low birth weight (1,882 g) and was found to be thrombo cytopenic and leukocytopenic (fig. 2). This thrombocytopenia Fig. 2. Clinical course of the infant after birth, r-gl = ywas successfully treated with high-dose y-globulin (400 mg/kg/day Globulin.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 10:25:41 AM
Fig. 1. Clinical course of the patient. Plate let-associated IgG (PAIgG) is expressed by PLT ng/10xl056 platelets (normal
