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Year : 2013  |  Volume : 56  |  Issue : 4  |  Page : 453-456
Simultaneous occurrence of chronic myeloid leukemia and chronic lymphocytic leukemia: Report of an unusual case

1 Department of Hematology, Sanjay Gandhi Post Graduate Institute of medical sciences, Lucknow, India
2 Departments of Pathology, Rajiv Gandhi Cancer Institute & Research Centre, Rohini, New Delhi, India
3 Department of Biotechnolocy, Amity University, Noida, India

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Date of Web Publication18-Jan-2014


The coexistence of chronic myeloid leukaemia(CML) and chronic lymphocytic leukemia(CLL) has been reported occasionally in literature, with only seven cases of simultaneous occurrence of these two diseases. We present here a case of 57 yr male patient where a complete blood count and differential done using volume conductivity scatter (VCS) technology suggested a diagnosis of CML with CLL. It was further confirmed by immunophneotyping and cytogenetic analysis. The patient was started on tyrosine kinase inhibitor, 400 mg once daily. Four months after the treatment, patient is doing fine with a count of 22 × 10 9 /L and 64% lymphocytes.

Keywords: Chronic lymphocytic leukemia, chronic myeloid leukemia, immunophenotype, cytogentics, volume conductivity scatter

How to cite this article:
Rahman K, George S, Mangal S, Mehta A. Simultaneous occurrence of chronic myeloid leukemia and chronic lymphocytic leukemia: Report of an unusual case. Indian J Pathol Microbiol 2013;56:453-6

How to cite this URL:
Rahman K, George S, Mangal S, Mehta A. Simultaneous occurrence of chronic myeloid leukemia and chronic lymphocytic leukemia: Report of an unusual case. Indian J Pathol Microbiol [serial online] 2013 [cited 2022 Jul 4];56:453-6. Available from: https://www.ijpmonline.org/text.asp?2013/56/4/453/125369

   Introduction Top

The coexistence of chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) is an uncommon event with only 21 cases reported in literature until date. [1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20] These two diseases can occur either sequentially, or simultaneously as in the present case. High risk of developing a second malignancy associated with an immune modulation and associated therapeutic regimen, have been proposed as the cause for sequential development of these diseases. For simultaneous occurrence, a possibility of common stem cell origin for these two diseases has been suggested. The first investigation to be done in these cases is a complete blood count (CBC) with differential leukocyte count (DLC). Automated analyzers can indicate the presence of a proliferative neoplasm with a suggestion of myeloid or lymphoid origin. In addition, they can very well predict the morphology of the neoplastic cells. We present here a case of 57-year-old male patient who presented to us with a weakness and an abdominal discomfort. CBC done with the automated analyzer using VCS technology for differential suggested a proliferative neoplasm with both myeloid and lymphoid component. Morphological examination of peripheral smears and bone marrow along with immunophenotypic finding and cytogenetic analysis confirmed the simultaneous occurrence of CML and CLL in this case.

   Case Report Top

We report a case of a 57-year-old male, diabetic, normotensive patient presented to us with the complaint of weakness and an abdominal discomfort for 15 days. On examination, pallor was present but no icterus. Splenomegaly was seen, which was 3 cm below the costal margin. No lymphadenopathy or any other significant findings were noted. CBC done with automated analyzer using VCS technology for the differential count showed a hemoglobin of 102 g/L, total leukocyte count of 131 × 10 9 /L, platelet count of 436 × 10 9 /L. DLC given by the analyzer was polymorphs-66.7, lymphocytes-26.6, monocytes-3.0, basophil-2.2, eosinophil-0.5. The mean volume of lymphocytes was lower than that of the control group (60 vs. 78 $ ) with little variation in size, as indicated by slightly higher standard deviation of volume index (SDVI). Similarly, the mean volume of neutrophils was also increased (172.8 vs. 149.2 $ ) with very high SDVI, indicating the presence of the whole spectrum of immature myeloid cells. Analyzing all these findings, we concluded that we were dealing with a proliferative disorder which was both myeloid as well as lymphoid and showed the presence of myeloid precursor, basophils and small sized lymphoid cells. Peripheral smear shows the presence of leukocytosis with the shift to left and basophilia. Lymphocytosis was also noted, which was of small size and showed the presence of hyper-condensed chromatin. Bone marrow examination showed the presence of hypercellular packed particles with cellular trails. There was myeloid preponderance, shift to left and basophilia with a myeloid erythroid ratio of 30:1. Micromegakaryocytes were seen along with occasional sea blue histiocytes. An additional finding was the presence of approximately 30% small-sized atypical lymphoid cells with hyper-condensed chromatin. Bone marrow biopsy showed a hypercellular marrow with 95% of cellularity showing myeloid and megakaryocytic preponderance. Two CD20 positive lymphoid nodules were noted [Figure 1]. Immunophenotypic analysis by flow cytometry was performed on peripheral blood which showed the presence of 31% lymphoid cells with co expression of CD19, CD5, CD23 and FMC 7 negativity [Figure 2]. Conventional karyotype done on bone marrow sample showed t(9;22)(q34;q11), Philadelphia positive.
Figure 1: Leishman stained peripheral smear – leukocytosis with shift to left , basophilia and lymphocytosis (a, ×20). Small sized atypical lymphoid cells with patchy hypercondensed chromati n (b, ×100). May-Grünwald Giemsa stained bone marrow aspirati on - hypercellular packed parti cles with cellular trails (c, ×2). Myeloid precursors along with similar small sized atypical lymphoid cells noted (d, ×100). H and E stained marrow biopsy - hypercellular marrow showing myeloid preponderance along with two lymphoid nodules (e, ×2). The nodule is positive for CD20 (f, ×2)

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Figure 2: Immunophenotyping done using four color flow cytometry showed approximately 30% lymphoid cells to co express CD19, CD5, CD23 along with negati vity for FMC7, indicati ng them to be chronic lymphocyti c leukemia

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Based on all the above findings, a final diagnosis of concurrent CML and CLL was made. Patient was started on a tyrosine kinase inhibitor (imatinib) in a dose of 400 mg OD. Patient is on regular follow-up and is doing fine with a count of 22 × 10 9 /L and 64% lymphocytes.

   Discussion Top

Coexistence of myeloproliferative and lymphoproliferative disorders in the same patient is uncommon. Even rare is the concordant occurrence of CML and CLL which can be found as isolated case reports in the literature. [1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20] Leukemogenic effect of therapy and an impaired immune response in cases of CLL have been suggested as the possible risk factors for development of second malignancy. [21] Although the second malignancy is usually a non-hematological one, association with other hematological neoplasm has also been reported. On the other hand, patients with CML have a natural history of developing a blast crisis and are rarely associated with the development of a second malignancy. However, it has also been documented that BCR-ABL transformed cells secrete cytokines like IL3 which increases the production of B lymphoid cells from human CD34 + /CD38 progenitor cells and in turn may lead to the development of CLL. [22]

These probable explanations do not hold true for the cases where these two chronic neoplasms have occurred simultaneously without any prior history of one or the other disease. In such a situation, the concordant occurrence can either be a coincidental finding, or it can be presumed that these neoplasms originate from a unique stem cell capable of differentiating into two different cell lines. Molecular studies aimed at ascertaining such a possibility are scarce and have found the separate origins of these two diseases. BCR/ABL rearrangement could be detected in granulocytic component only, but not in the mononuclear cell fraction, probably composed mainly of CLL cells. On the contrary, characteristic band corresponding to a monoclonal lymphoid population after JH rearrangement analysis could be seen in the lymphoid-enriched cellular component, but not in the myeloid fraction. [2],[23],[24]

After an extensive search, only 21 cases with a concurrent occurrence of CML and CLL could be found in the literature. Most of the cases have CLL preceding CML (n = 11) with an interval between the two diseases ranging from 2 months to 84 months.

Cases with simultaneous are less frequent (n = 7). Three cases of CLL following CML by duration ranging from 20 to 74 months have been reported. A brief account of these cases has been mentioned in [Table 1].
Table 1: Pati ents with concordant CML and CLL, described in literature

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The present case has leukocytosis at presentation with 30% of lymphocytes and shift to left. Automated analyzer with VCS technology for the differential count directed us to perform ancillary investigation to prove the co-existence of these two diseases. CML was the obvious finding, but the nature of lymphocytosis was to be determined. VCS parameters of a low mean volume with a slightly higher SDVI suggested the neoplastic nature of the lymphocytes. As suggested by Silva et al. [25] these findings favor a CLL over reactive lymphocytosis. Peripheral smear, bone marrow aspirate, bone marrow biopsy, immunophenotypic evaluation and cytogenetic analysis proved this case as concurrent CML and CLL. Patient was started on 400 mg OD imatinib with regular follow-up. 4 months after the treatment, patient is doing fine with a count of 22 × 10 9 /L and 64% lymphocytes.

   Conclusion Top

Our case is an addition to the scarce literature on concurrent occurrence of CML and CLL which can be either sequential or simultaneous. IPA, cytogenetic and molecular analysis of these cases has revealed a rare event of leukemogenesis caused by a biclonal evolution. In addition, our report points out the importance of automated CBC analyzer with VCS parameter in preliminary diagnosis where this rare possibility can be suggested and ancillary investigation advised for further work-up.

   References Top

1.Leoni F, Ferrini PR, Castoldi GL, Pata M, Del Prete GF, Tomasi P. Simultaneous occurrence of chronic granulocytic leukemia and chronic lymphoid leukemia. Haematologica 1987;72:253-6.  Back to cited text no. 1
2.Maher VE, Gill L, Townes PL, Wallace JE, Savas L, Woda BA, et al. Simultaneous chronic lymphocytic leukemia and chronic myelogenous leukemia. Evidence of a separate stem cell origin. Cancer 1993;71:1993-7.  Back to cited text no. 2
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4.Vilpo JA, Klemi P, Lassila O, Schröder J, de la Chapelle A. Transformation in chronic granulocytic leukaemia. Different blast cell clones in different anatomical sites. Acta Haematol 1979;62:247-50.  Back to cited text no. 4
5.Esteve J, Cervantes F, Rives S, Rozman M, Zarco MA, Montserrat E. Simultaneous occurrence of B-cell chronic lymphocytic leukemia and chronic myeloid leukemia with further evolution to lymphoid blast crisis. Haematologica 1997;82:596-9.  Back to cited text no. 5
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14.Nanjangud GJ, Saikia TK, Chopra H, Kadam PR, Advani SH. Development of Ph positive chronic myeloid leukemia in a patient with chronic lymphocytic leukemia treated with total body irradiation: A rare association. Leuk Lymphoma 1996;22:355-9.  Back to cited text no. 14
15.Mossafa H, Fourcade C, Pulic M, Jary L, Cheze S, Szpiro-Tapia S, et al. Chronic lymphocytic leukemia associated with myelodysplastic syndrome and/or chronic myeloid leukemia: Evidence for independent clonal chromosomal evolution. Leuk Lymphoma 2001;41:337-41.  Back to cited text no. 15
16.Ramanarayanan J, Dunford LM, Baer MR, Sait SN, Lawrence W, McCarthy PL. Chronic myeloid leukemia after treatment of lymphoid malignancies: Response to imatinib mesylate and favorable outcomes in three patients. Leuk Res 2006;30:701-5.  Back to cited text no. 16
17.Hattori H, Kuwayama M, Kotake T, Karasuno T. A case of chronic myeloid leukemia occurring during treatment for chronic lymphocytic leukemia. Gan To Kagaku Ryoho 2011;38:333-6.  Back to cited text no. 17
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19.Gargallo P, Cacchione R, Chena C, Dupont J, Garay G, Riveros D, et al. Chronic lymphocytic leukemia developing in a patient with chronic myeloid leukemia: Evidence of distinct lineage-associated genomic events. Cancer Genet Cytogenet 2005;161:74-7.  Back to cited text no. 19
20.Bhagavathi S, Borromeo V, Desai H, Crisan D. Case report and literature review: A rare patient with chronic myeloid leukemia and chronic lymphocytic leukemia. Ann Clin Lab Sci 2008;38:405-9.  Back to cited text no. 20
21.Bartik MM, Welker D, Kay NE. Impairments in immune cell function in B cell chronic lymphocytic leukemia. Semin Oncol 1998;25:27-33.  Back to cited text no. 21
22.Crooks GM, Hao QL, Petersen D, Barsky LW, Bockstoce D. IL-3 increases production of B lymphoid progenitors from human CD34+CD38- cells. J Immunol 2000;165:2382-9.  Back to cited text no. 22
23.Browett PJ, Pattinson J, Pinkney J, Hoffbrand AV, Norton JD. Gene probe analysis demonstrates independent clonal evolution of co-existent chronic myeloid and chronic lymphocytic leukaemia. Eur J Haematol 1988;40:181-4.  Back to cited text no. 23
24.Zollino M, Genuardi M, Tanci P, Mango G, Rumi C, Mancini R, et al. Chronic myelogenous leukemia in the course of chronic lymphocytic leukemia: Evidence for an independent clonal origin. Leuk Res 1991;15:269-73.  Back to cited text no. 24
25.Silva M, Fourcade C, Fartoukh C, Lenormand B, Buchonnet G, Callat MP, et al. Lymphocyte volume and conductivity indices of the haematology analyser Coulter GEN.S in lymphoproliferative disorders and viral diseases. Clin Lab Haematol 2006;28:1-8.  Back to cited text no. 25

Correspondence Address:
Khaliqur Rahman
Assistant Professor, Department of Hematology, Sanjay Gandhi Post Graduate Institute of medical sciences, Lucknow - 226 014
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.125369

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  [Figure 1], [Figure 2]

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