Unexpected pancytopenia following treatment of acute lymphoblastic leukemia
1
Unexpected pancytopenia following treatment of acute lymphoblastic leukemia Andrew Innes, 1 Philippa C. May, 1 Jir ˇı ´ Pavlu ˚, 1 and Barbara J. Bain 2 A 55-year-old woman presented with lethargy and spontaneous bruising. A full blood count showed: white cell count (WBC) 1.6 x 10 9 /l, hemoglobin concentration (Hb) 7.8 g/dl, platelet count 35 x 10 9 /l and neutrophil count 0.1 x 10 9 /l. There were blast cells in the peripheral blood. A diagnosis of B-lineage acute lymphoblastic leukemia (ALL) was made, the immunophenotype being that of common ALL. Cytogenetic analysis was normal. The patient entered complete remission with induction chemotherapy according to the UKALL XII protocol. She received consolidation chemotherapy and cranial irradiation followed by maintenance chemotherapy (mercaptopurine 50 mg daily, methotrexate 15 mg weekly and vincris- tine 2 mg 3-monthly) plus intrathecal cytarabine 3-monthly. Twenty six months after presentation while still on maintenance therapy the patient became pancytopenic; WBC 0.9 x 10 9 /l, Hb 8 g/dl, platelet count 20 x 10 9 /l and neutrophil count 0.6 x 10 9 /l. A bone marrow aspirate showed markedly meg- aloblastic erythropoiesis with giant metamyelocytes and giant band forms. However there were also 8% blast cells (Image, arrows), which immunophenotypically typed as myeloid. Cytogenetic analysis showed 46,XX,t(6;9)(p23;q34)[19]/46,XX[1]. A diagnosis of therapy-related myelodysplastic syndrome (t-MDS) was made and the weekly methotrexate was stopped. Over the next two and a half months there was progression to 88% bone marrow blasts, accompanied by cytogenetic evo- lution to 46,XX,t(6;9)(p23;q34)[2]/48,idem,113,115[9]. At this stage there was normoblastic erythropoiesis with no giant metamyelocytes. The patient proved to be refractory to chemotherapy. Our initial suspicion on discovering markedly megaloblastic erythropoiesis was that the pancytopenia was the result of methotrexate toxicity. However the presence of increased blast cells indicated other possibilities, either t-MDS or early relapse of ALL. Acute myeloid leukemia (AML) with t(6;9)(p23;q34) resulting in the DEK-NUP214 fusion gene is a recog- nised form of t-AML. Megaloblastosis can be a feature of AML but in this patient, since erythropoiesis became normoblas- tic on methotrexate withdrawal, it was indeed a drug-induced megaloblastosis. The pancytopenia, however, was the result of an emerging t-AML, probably resulting from etoposide or daunorubicin of which she had received total doses of 340 mg/m 2 and 2.7 g respectively. Alkylating agents have also been followed by t-AML with t(6;9) but cyclophosphamide is not a potent leukemogen. 1 Department of Haematology, Imperial College Healthcare NHS Trust, Ham- mersmith Hospital, Du Cane Road, London W12 0HS 2 Imperial College Faculty of Medicine, Department of Haematology, St Mary’s Hospital, London W2 1NY *Correspondence to: Imperial College Faculty of Medicine, Department of Haematology, St Mary’s Hospital, London W2 1NY. E-mail: [email protected] Received for publication 26 July 2011; Accepted 26 July 2011 Am. J. Hematol. 87:412, 2012. Published online 29 July 2011 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/ajh.22159 AJH Educational Material Morphology Update V V C 2011 Wiley Periodicals, Inc. American Journal of Hematology 412 http://wileyonlinelibrary.com/cgi-bin/jhome/35105
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Transcript of Unexpected pancytopenia following treatment of acute lymphoblastic leukemia
Unexpected pancytopenia following treatment of acutelymphoblastic leukemia
Andrew Innes,1 Philippa C. May,1 Jirı Pavlu,1 and Barbara J. Bain2
A 55-year-old woman presented with lethargy and spontaneous bruising. A full blood count showed: white cell count(WBC) 1.6 x 109/l, hemoglobin concentration (Hb) 7.8 g/dl, platelet count 35 x 109/l and neutrophil count 0.1 x 109/l. Therewere blast cells in the peripheral blood. A diagnosis of B-lineage acute lymphoblastic leukemia (ALL) was made, theimmunophenotype being that of common ALL. Cytogenetic analysis was normal. The patient entered complete remissionwith induction chemotherapy according to the UKALL XII protocol. She received consolidation chemotherapy and cranialirradiation followed by maintenance chemotherapy (mercaptopurine 50 mg daily, methotrexate 15 mg weekly and vincris-tine 2 mg 3-monthly) plus intrathecal cytarabine 3-monthly.Twenty six months after presentation while still on maintenance therapy the patient became pancytopenic; WBC 0.9 x
109/l, Hb 8 g/dl, platelet count 20 x 109/l and neutrophil count 0.6 x 109/l. A bone marrow aspirate showed markedly meg-aloblastic erythropoiesis with giant metamyelocytes and giant band forms. However there were also 8% blast cells (Image,arrows), which immunophenotypically typed as myeloid. Cytogenetic analysis showed 46,XX,t(6;9)(p23;q34)[19]/46,XX[1].A diagnosis of therapy-related myelodysplastic syndrome (t-MDS) was made and the weekly methotrexate was stopped.Over the next two and a half months there was progression to 88% bone marrow blasts, accompanied by cytogenetic evo-lution to 46,XX,t(6;9)(p23;q34)[2]/48,idem,113,115[9]. At this stage there was normoblastic erythropoiesis with no giantmetamyelocytes. The patient proved to be refractory to chemotherapy.Our initial suspicion on discovering markedly megaloblastic erythropoiesis was that the pancytopenia was the result of
methotrexate toxicity. However the presence of increased blast cells indicated other possibilities, either t-MDS or earlyrelapse of ALL. Acute myeloid leukemia (AML) with t(6;9)(p23;q34) resulting in the DEK-NUP214 fusion gene is a recog-nised form of t-AML. Megaloblastosis can be a feature of AML but in this patient, since erythropoiesis became normoblas-tic on methotrexate withdrawal, it was indeed a drug-induced megaloblastosis. The pancytopenia, however, was the resultof an emerging t-AML, probably resulting from etoposide or daunorubicin of which she had received total doses of 340mg/m2 and 2.7 g respectively. Alkylating agents have also been followed by t-AML with t(6;9) but cyclophosphamide is nota potent leukemogen.
1Department of Haematology, Imperial College Healthcare NHS Trust, Ham-mersmith Hospital, Du Cane Road, London W12 0HS2Imperial College Faculty of Medicine, Department of Haematology, StMary’s Hospital, London W2 1NY
*Correspondence to: Imperial College Faculty of Medicine, Department ofHaematology, St Mary’s Hospital, London W2 1NY. E-mail: [email protected]
Received for publication 26 July 2011; Accepted 26 July 2011
Am. J. Hematol. 87:412, 2012.
Published online 29 July 2011 in Wiley Online Library (wileyonlinelibrary.com).DOI: 10.1002/ajh.22159
AJH Educational Material Morphology Update
VVC 2011 Wiley Periodicals, Inc.
American Journal of Hematology 412 http://wileyonlinelibrary.com/cgi-bin/jhome/35105
