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An unusual case of phenotype switch between AML FAB subtypes.

Das A, Singh A, Gajendra S, Gupta R, Sazawal S, Seth R - Clin Case Rep (2014)

Bottom Line: Phenotypic switch between any leukemia subtypes is of concern to a treating physician and more so, in acute myelocytic leukemia (AML) as the mechanisms for switch and subsequent chemotherapy regimen to be used remain unclear.AML-non-M3 from AML-M3 subtype needs special mention as this has been unheard off.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, All India Institute of Medical Sciences New Delhi, India.

ABSTRACT
Phenotypic switch between any leukemia subtypes is of concern to a treating physician and more so, in acute myelocytic leukemia (AML) as the mechanisms for switch and subsequent chemotherapy regimen to be used remain unclear. AML-non-M3 from AML-M3 subtype needs special mention as this has been unheard off.

No MeSH data available.


Related in: MedlinePlus

Peripheral blood smear showing abnormal promyelocytes at diagnosis (Jenner and Giemsa, 1000×).
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fig01: Peripheral blood smear showing abnormal promyelocytes at diagnosis (Jenner and Giemsa, 1000×).

Mentions: A 5-year-old girl presented with fever, neck swelling, and weight loss for 2 months in April 2011 for which she was started on antitubercular drugs by a local physician. On examination, she had pallor, bilateral cervical lymphadenopathy, and hepatosplenomegaly (liver 3 cm and spleen 3 cm below costal margin). There were no signs of bleeding, focal neurological deficit, or gum hypertrophy. The hemoglobin was 71 gm/L, total leukocyte count was 8.1 × 109/L, and platelet count was 31 × 109/L. d-dimer test, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were within normal limits. Peripheral blood smear showed 80% abnormal promyelocytes which were immunopositive for cMPO, CD45, CD33, CD117, CD2, CD13 (dim), and CD38 (dim) and immunonegative for CD34, HLADR, cCD79a, CD19, CD18, CD4, CD7, and cCD3. Bone marrow (BM) aspiration revealed near total replacement by abnormal promyelocytes (Fig.1). Morphological and immunophenotypic features were consistent with APML microgranular variant. No abnormal cells were noted on cerebrospinal fluid cytology. RT-PCR for PML/RARα rearrangement showed a positive result. The patient was started on arsenic monotherapy (0.15 mg/kg per day) and after 60 days of induction, morphological remission in BM and absence of PML/RARα transcripts on RT-PCR were reported. Induction was followed by one cycle of consolidation of 28 days with arsenic (0.15 mg/kg per day) and six cycles of maintenance; monthly cycle of arsenic for 10 days/month (0.15 mg/kg per day) and intrathecal methotrexate on day 1 (8 mg) till March 2012. The child was apparently well for 1 month, after which she again presented with fever. Five percent abnormal promyelocyteson peripheral blood smear and presence of PML/RARα transcripts on RT-PCR were noted. At this time, treatment was initiated with ATRA (45 mg/m2 per day) and daunomycin (1.5 mg/kg per day). Morphological remission in BM was reported after completion of 3 months of induction and thereafter consolidation with ATRA (0.15 mg/kg per day), daunorubicin, and cytarabine on day 1. Within 2 months of consolidation phase, patient relapsed again and the BM at this time was replaced by blasts which were immunopositive for cMPO, CD45, CD34, CD13, CD33, CD117, CD15, CD11b, CD56, CD19, CD64, CD2, CD65, CD7, HLADR, CD9, CD4, and CD133 and negative for CD38, cCD79a, and cCD3, suggestive of AML-non-M3 (Fig.2). PML/RARα by RT-PCR was negative. A diagnosis of switch to AML-non-M3 from AML-M3 was made. The prognosis was discussed with the family and the child was started on Medical Research Council's 10th AML (MRC AML10) protocol. The child succumbed to death after 2 months due to sepsis (febrile neutropenia), refractory shock, and ongoing myocardial dysfunction for which the child was on cardioprotective drugs.


An unusual case of phenotype switch between AML FAB subtypes.

Das A, Singh A, Gajendra S, Gupta R, Sazawal S, Seth R - Clin Case Rep (2014)

Peripheral blood smear showing abnormal promyelocytes at diagnosis (Jenner and Giemsa, 1000×).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4352367&req=5

fig01: Peripheral blood smear showing abnormal promyelocytes at diagnosis (Jenner and Giemsa, 1000×).
Mentions: A 5-year-old girl presented with fever, neck swelling, and weight loss for 2 months in April 2011 for which she was started on antitubercular drugs by a local physician. On examination, she had pallor, bilateral cervical lymphadenopathy, and hepatosplenomegaly (liver 3 cm and spleen 3 cm below costal margin). There were no signs of bleeding, focal neurological deficit, or gum hypertrophy. The hemoglobin was 71 gm/L, total leukocyte count was 8.1 × 109/L, and platelet count was 31 × 109/L. d-dimer test, prothrombin time (PT), and activated partial thromboplastin time (aPTT) were within normal limits. Peripheral blood smear showed 80% abnormal promyelocytes which were immunopositive for cMPO, CD45, CD33, CD117, CD2, CD13 (dim), and CD38 (dim) and immunonegative for CD34, HLADR, cCD79a, CD19, CD18, CD4, CD7, and cCD3. Bone marrow (BM) aspiration revealed near total replacement by abnormal promyelocytes (Fig.1). Morphological and immunophenotypic features were consistent with APML microgranular variant. No abnormal cells were noted on cerebrospinal fluid cytology. RT-PCR for PML/RARα rearrangement showed a positive result. The patient was started on arsenic monotherapy (0.15 mg/kg per day) and after 60 days of induction, morphological remission in BM and absence of PML/RARα transcripts on RT-PCR were reported. Induction was followed by one cycle of consolidation of 28 days with arsenic (0.15 mg/kg per day) and six cycles of maintenance; monthly cycle of arsenic for 10 days/month (0.15 mg/kg per day) and intrathecal methotrexate on day 1 (8 mg) till March 2012. The child was apparently well for 1 month, after which she again presented with fever. Five percent abnormal promyelocyteson peripheral blood smear and presence of PML/RARα transcripts on RT-PCR were noted. At this time, treatment was initiated with ATRA (45 mg/m2 per day) and daunomycin (1.5 mg/kg per day). Morphological remission in BM was reported after completion of 3 months of induction and thereafter consolidation with ATRA (0.15 mg/kg per day), daunorubicin, and cytarabine on day 1. Within 2 months of consolidation phase, patient relapsed again and the BM at this time was replaced by blasts which were immunopositive for cMPO, CD45, CD34, CD13, CD33, CD117, CD15, CD11b, CD56, CD19, CD64, CD2, CD65, CD7, HLADR, CD9, CD4, and CD133 and negative for CD38, cCD79a, and cCD3, suggestive of AML-non-M3 (Fig.2). PML/RARα by RT-PCR was negative. A diagnosis of switch to AML-non-M3 from AML-M3 was made. The prognosis was discussed with the family and the child was started on Medical Research Council's 10th AML (MRC AML10) protocol. The child succumbed to death after 2 months due to sepsis (febrile neutropenia), refractory shock, and ongoing myocardial dysfunction for which the child was on cardioprotective drugs.

Bottom Line: Phenotypic switch between any leukemia subtypes is of concern to a treating physician and more so, in acute myelocytic leukemia (AML) as the mechanisms for switch and subsequent chemotherapy regimen to be used remain unclear.AML-non-M3 from AML-M3 subtype needs special mention as this has been unheard off.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, All India Institute of Medical Sciences New Delhi, India.

ABSTRACT
Phenotypic switch between any leukemia subtypes is of concern to a treating physician and more so, in acute myelocytic leukemia (AML) as the mechanisms for switch and subsequent chemotherapy regimen to be used remain unclear. AML-non-M3 from AML-M3 subtype needs special mention as this has been unheard off.

No MeSH data available.


Related in: MedlinePlus