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Year : 2020  |  Volume : 11  |  Issue : 1  |  Page : 21-24

The intriguing occurrence of Acute Myeloid Leukemia in a case of Acute Lymphoblastic leukemia:Report of two cases

1 Department of Laboratory Medicine, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
2 Department of Medical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India

Date of Submission26-Sep-2019
Date of Acceptance18-Nov-2019
Date of Web Publication13-Mar-2020

Correspondence Address:
Dr. Manasi Chetan Mundada
Department of Laboratory Medicine, Basvatarakam Indo American Cancer Hospital and Research Institute, Road No. 10, Banjara Hills, Hyderabad - 500 034, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/joah.joah_64_19

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The aim of this study is to study the two cases of acute lymphoblastic leukemia (ALL) who relapsed as acute myeloid leukemia (AML). Presented here are reports of two cases of pediatric ALL who developed change of lineage to AML at relapse. This change in phenotype, which involves the conversion of one phenotype to other phenotype during the course of disease or at relapse is a rare phenomenon rarely described in literature. The immunophenotypic and molecular findings are described. The present study emphasizes the need of immunophenotyping and molecular workup at relapse. Also adds to the repertoire of the published literature on this rare entity.

Keywords: Acute lymphoblastic leukemia, acute myeloid leukemia, immunophenotyping, lineage change, molecular finding

How to cite this article:
Mundada MC, Ahmed F, Pasam MK, Murthy S, Santa A, Patil V. The intriguing occurrence of Acute Myeloid Leukemia in a case of Acute Lymphoblastic leukemia:Report of two cases. J Appl Hematol 2020;11:21-4

How to cite this URL:
Mundada MC, Ahmed F, Pasam MK, Murthy S, Santa A, Patil V. The intriguing occurrence of Acute Myeloid Leukemia in a case of Acute Lymphoblastic leukemia:Report of two cases. J Appl Hematol [serial online] 2020 [cited 2022 Dec 5];11:21-4. Available from: https://www.jahjournal.org/text.asp?2020/11/1/21/280546

  Introduction Top

Lineage switch in acute leukemia is a rarely described entity in literature. It involves the conversion of one phenotype to other during disease or at relapse. Different case scenarios are described in literature wherein B-lymphoblastic leukemia (B-ALL) turned to acute myeloid leukemia (AML) and vice versa. These are more commonly described in the pediatric population, although cases in adults are also reported. Here, we present two interesting cases of phenotype switch.

  Case Reports Top

Case 1

In the year 2014, a 3-year-old girl was evaluated elsewhere for fever on and off for 3 months. Examination findings revealed mild hepatosplenomegaly. Peripheral blood examination showed leukocytosis with the presence of blast, morphologically lymphoblast and negative for myeloperoxidase (MPO) cytochemical stain. Immunophenotyping characteristics are enumerated in [Table 1]. The diagnosis of B-ALL was rendered. Cytogenetics showed a normal 46XX karyotype; however, fluorescence in situ hybridization (FISH) revealed ETV6-RUNX 1 t(12,21) (p13.2;q22.1) translocation in 55% of the cells. Other mutation BCR-ABL, t(1,19), and MLL tested were negative by FISH. The patient was started on BFM95 protocol (prednisolone, daunorubicin, vincristine, L-asparginase, and methotrexate). Remission was documented at the end of induction phase. The patient completed the consolidation and maintenance phase in 2016. In 2019, the patient presented at our center with fever, weakness, and loss of appetite for duration of 20 days. Peripheral blood examination showed 14% blasts and 2% basophilia [Figure 1]a. Immunophenotyping showed two populations of CD45-positive cells showing myeloid antigens comprising of CD13, CD33, MPO. Aberrant expression of CD79a and CD22 was seen on one population, whereas on other B markers were negative [Figure 2]. Cytogenetic evaluation revealed 46XX, add (17) (p13). Polymerase chain reaction (PCR) was done for BCR-ABL1, t(8,21), t(9,11), Inv16, flt3, Nucleophosmin 1 NPM was negative. The patient was started on FLAG protocol (Fludarabin, cytarabin, and granulocyte colony-stimulating factor [G-CSF]). The patient did not achieve remission at the end of induction phase. However, developed febrile neutropenia and succumbed to the infection.
Table 1: Synopsis and chronological sequence in the twin cases

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Figure 1: (a) Case 1 showing undifferentiated blast morphology, basophil (arrow) also included in the field (Leishman, ×400). (b) Case 2 showing predominance of blasts, cytoplasm shows the presence of fine granules (arrow) (Leishman, ×400)

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Figure 2: Flowcytometry results of case one, wherein the gated blast population (red and green) show positive myeloid markers. Only red population shows aberrant CD22 and CD79a expression

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Case 2

In 2015, a 5-year-old boy was evaluated elsewhere for on and off episodes of fever of 1-month duration. Immunophenotyping performed on peripheral blood showed B-ALL. Bone marrow showed 30% blasts. The patient came to our hospital for treatment, chemotherapy with MCP 841 protocol was initiated (Vincristine Daunomycin Methotrexate). Postinduction the patient achieved remission and later completed the consolidation phase with few episodes of hospitalization for fever and neutropenia. The maintenance regime was started with 6 mercaptopurine, methotrexate, cyclophosphamide followed by vincristine + L-asparaginase, which ended in May 2018. Subsequently, the patient developed leukopenia. He was treated with G-CSF/blood products/IV antibiotics and supportive care. The patient had persisting leucopenia for a period of 5 months duration and was admitted at our hospital for headache and vomiting for supportive care. Peripheral blood examination revealed 12% blasts. Magnetic resonance imaging brain was suggestive of focal cerebritis/infiltration, CSF examination was normal. Bone marrow examination showed a hypercellular marrow with 8% blasts. The blasts were negative for cytochemical stains MPO and periodic acid-schiff. The patient was advised weekly follow-up with supportive treatment. He defaulted and presented back to the hospital after 20 days, this time the peripheral blood examination showed rise in the blast count. Bone marrow done showed 81% blasts [Figure 1]b. Immunophenotyping done on peripheral blood revealed AML. None of the B- and T-cell markers were positive [Table 1]. Cytogenetics showed 46XY, der (18) dup (18) (q21q23) in all the 20 cells analyzed. Induction chemotherapy with mitoxantrone + cytarabine was started. However, the patient failed to achieve remission and reinduction was done. Simultaneously, the patient was counseled for stem cell transplant. At present, the patient is undergoing his second induction cycle.

  Results Top

In case 1, the switch from ALL to AML occurred at 4 1/2 years after the initiation of therapy. Morphologically, the FAB subtype was AML-M0. Basophilia was observed on smear at relapse; however, PCR was negative for major, minor, and micro BCR-ABL transcripts. The Immunophenotyping (IPT) showed expression of myeloid markers with one clone showing B lymphoid markers CD22 and CD79a and gain of mutation as seen on karyotyping. However, initially seen translocation (12,21) could not be evaluated at relapse. Prognostic panel for AML by PCR was negative.

In case 2, the switch happened at 3 years after initiation of therapy. Morphologically, the blasts were of undifferentiated type. Immunophenotyping showed myeloid phenotype. This case showed a transition into an myelodysplastic syndrome (MDS) such as stage with peripheral cytopenia, hypercellular marrow with 8% blasts, and dysplasia noted in two lineages before a florid leukemic phase developed; however, cytogenetic evaluation on marrow was not done. Karyotyping done at relapse showed derivative 18 duplication.

  Discussion Top

ALL represents the most common type of leukemia in children. The relapse of disease whenever occurs, the phenotype remains the same. Lineage switch at relapse though described in literature is a rare occurrence with the reported incidence being 6%–8%.[1] More commonly, lineage switch described is ALL transforming to AML and mostly seen in the pediatric population,[2],[3] which was also seen in the two cases described in the present study [Table 1].

Various hypothesis have been laid to explain the phenomenon of lineage switch, most common ones being chemotherapy-induced selection of subclone resistant to therapy which proliferates, leading to phenotypic switch (which might explain the aberrant B markers in case 1), pluripotent nature/plasticity of stem cells capable of multilineage differentiation in accordance to external stimuli and intrinsic environmental factors.[1],[4] Mutations occurring in very immature bipotential progenitor stem cells have also been suggested as a mechanism responsible for the phenotypic switch. Hence, high association of MLL gene abnormalities with lineage switches point to origin of MLL-ALL from immature precursors.

In case 1, the presence of basophilia raised the suspicion of association with chronic myeloid leukemia, in which sequential myeloid and lymphoid blast crisis is known,[5] however was ruled out by real-time-PCR for BCR-ABL. Some authors have suggested the phenotypic switch as a part of the biologic spectrum of mixed phenotypic leukemia.[4],[6]

Transitional MDS like disease on marrow morphology seen in the second case, Wu et al.[7] have described similar features in their two cases of phenotypic switch, wherein the initial karyotype associated with B-ALL was a complex followed by abnormalities indicative of MDS. Both these entities are associated with bad prognosis.[4],[8]

The authors cannot conclusively rule out therapy-related myeloid neoplasm in both cases, as the lineage switch occurred late in the course of disease 4½ and 3 years, respectively. However scenarios like the present one are described in literature, although rare.[4] There is no clear evidence as to pointers at differentiating a lineage switch from therapy-related AML except presence of the initially described cytogenetic/molecular abnormalities at relapse.[1] Therapy-related AML due to alkylating agents as in the present scenario are generally described at 5–7 years with high occurrence of molecular abnormalities such as monosomy 7 and del 5/monosomy 5,[9] which were not seen in our cases.

From the present study, we conclude the need of systematic approach in the diagnostic algorithm of acute leukemia. These cases reemphasize the need of immunophenotypic and molecular studies in relapse cases so as to better understand the evolving science behind these elusive case scenarios.

The present study adds to the repertoire of cases published since single-center large study is difficult in view of rarity of these cases.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Ruiz-Delgado GJ, Nu˜nez-Cortez AK, Olivares-Gazca JC, Fortiz YC, Ruiz-Arguelles A, Ruiz-Arguelles GJ. Lineage switch from acute lymphoblastic leukemia to myeloid leukemia. Med Univ 2017;19:27-31.  Back to cited text no. 1
Rossi JG, Bernasconi AR, Alonso CN, Rubio PL, Gallego MS, Carrara CA, et al. Lineage switch in childhood acute leukemia: An unusual event with poor outcome. Am J Hematol 2012;87:890-7.  Back to cited text no. 2
Stass S, Mirro J, Melvin S, Pui CH, Murphy SB, Williams D. Lineage switch in acute leukemia. Blood 1984;64:701-6.  Back to cited text no. 3
Dorantes-Acosta E, Pelayo R. Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity? Bone Marrow Research 2012;2012:18. https://doi.org/10.1155/2012/406796.  Back to cited text no. 4
Vardiman JW, Melo JV, Baccarani M, Radich JP, Kvanicka HM. Chronic myeloid leukemia, BCR-ABL1-positive. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al, editors. WHO Classification of Tumours of Hematopoietic and Lymphoid Tissues. Revised 4th ed. Lyon: IARC Press; 2017. p. 30-6.  Back to cited text no. 5
Park M, Koh KN, Kim BE, Im HJ, Jang S, Park CJ, et al. Lineage switch at relapse of childhood acute leukemia: A report of four cases. J Korean Med Sci 2011;26:829-31.  Back to cited text no. 6
Wu B, Jug R, Luedke C, Su P, Rehder C, McCall C, et al. Lineage switch between B-lymphoblastic leukemia and acute myeloid leukemia intermediated by “occult” myelodysplastic neoplasm: Two cases of adult patients with evidence of genomic instability and clonal selection by chemotherapy. Am J Clin Pathol 2017;148:136-47.  Back to cited text no. 7
Vardiman JW, Matutes E, Arber DA, Baumann I, Brunning RD, Kvasnicka HM,et al. Therapy related myeloid neoplasms. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th ed. Lyon: IARC Press; 2017. p. 153-5.  Back to cited text no. 8
Godley LA, Larson RA. Therapy-related myeloid leukemia. Semin Oncol 2008;35:418-29.  Back to cited text no. 9


  [Figure 1], [Figure 2]

  [Table 1]

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