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Year : 2019  |  Volume : 3  |  Issue : 3  |  Page : 59-61

Chronic myeloid leukemia with isolated central nervous system blast crisis a rare case presentation

Department of Radiation Oncology, Gujarat Cancer Research Institute, B J Medical College, Ahmedabad, Gujarat, India

Date of Web Publication27-Dec-2019

Correspondence Address:
Dr. Amit Kichloo
A 2 Amardeep Apartments, Civil Hospital Road, Ahmedabad, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/oji.oji_42_19

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Most cases of chronic myeloid leukemia (CML) manifest in chronic phase with high granulocyte count. Medical management with imatinib renders complete hematological and cytogenetic remission in almost all patients. Only 5%–10% of the patients progress to accelerated phase and terminal phase, i.e., blast crisis. Blast crisis is defined as the presence of ≥20% blasts in the bone marrow (BM) or peripheral blood, or a large focus of blasts in the BM, or presence of extramedullary infiltration with blast cells. The penetration of imatinib in the central nervous system (CNS) is very poor, and thus, CNS may become a sanctuary site in patients on prolonged treatment with imatinib. The CNS as a site of extramedullary crisis is extremely rare. We report a case of Philadelphia-positive CML on imatinib with cerebrospinal fluid cytology positive and approach to its management.

Keywords: Blast crisis, central nervous system, chronic myeloid leukemia

How to cite this article:
Kichloo A, Poddar J, Mankada S, Suryanarayana U. Chronic myeloid leukemia with isolated central nervous system blast crisis a rare case presentation. Oncol J India 2019;3:59-61

How to cite this URL:
Kichloo A, Poddar J, Mankada S, Suryanarayana U. Chronic myeloid leukemia with isolated central nervous system blast crisis a rare case presentation. Oncol J India [serial online] 2019 [cited 2020 Jun 4];3:59-61. Available from: http://www.ojionline.org/text.asp?2019/3/3/59/274096

  Introduction Top

Chronic myeloid leukemia (CML) is a chronic myeloproliferative disorder characterized by BCR-ABL reverse translocation between chromosomes 9 and 22. It consists of three stages, namely chronic phase, accelerated phase, and blast crisis. In patients, who are not the candidates for allogeneic marrow transplant, the treatment of choice is oral imatinib. Imatinib is a tyrosine kinase inhibitor which inhibits BCR-ABL transfusion signaling pathway. Few cases have been reported in literature of extramedullary crisis, i.e., presence of blastic infiltration other than bone marrow (BM), with central nervous system (CNS) being extremely rare.[1] It is clinically characterized by headache, vomiting, seizures, and focal neurological deficits. Herein, we report a case of CML in blast crisis in a 28-year-old male gradually developing CNS infiltration by blast cells diagnosed by cerebrospinal fluid (CSF) cytology.

  Case Report Top

A 28-year-old male presented at our institute with chief complaints of intermittent fever over last few days. Complete blood picture of the patient showed that hemoglobin: 14.1 gm%, total leukocyte count: 223,000/μL, platelets: 262,000/μL, metamyelocytes + myelocytes: 50%, blasts: 4%, absolute neutrophil count: 111,000/μL, absolute lymphocyte count: 45,000/μL, lactate dehydrogenase: 991 units/L, and serum calcium: 8.85 mg/dL. Ultrasonography of the abdomen and pelvis showed hepatomegaly (>21 cm) and massive splenomegaly (18 cm) with normal echo pattern. Thus, a provisional diagnosis of myeloproliferative disorder was made. BM examination revealed hypercellular marrow with marked proliferation of blast cells, i.e., 70%; these blasts had high nuclear: cytoplasmic ratio, moderate cytoplasm, fine nuclear chromatin, 0–2 nucleoli. Thus, diagnosis of CML in blast crisis was made.

Immunophenotyping study was done and the findings are depicted in [Table 1]. The blast cells expressed B-lymphoid markers CD19 along with CD34. Final diagnosis of CML with lymphoblastic crisis was made. Karyotyping showed t(9;22) (q34:11). Since the patient was not medically insured, so the percentage of transcripts was not performed both pre- and post-therapy. The patient was given four cycles of cyclophosphamide-vincristine-prednisolone, imatinib, and intrathecal methotrexate. The rationale behind using this protocol was that we started with the lowest efficacious dose of chemotherapy in view of poor performance status of the patient and evaluated for the response. After receiving chemotherapy, blood investigations were found to be within normal limit. Further, four cycles of vincristine and prednisolone chemotherapy along with imatinib were given as per our institutional protocol. Repeat BM biopsy showed no blasts cells. The patient was started on maintenance imatinib.
Table 1: Immunophenotyping study

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However, after receiving 7 months of oral imatinib therapy, the patient presented in the emergency room with headache and severe vomiting. Magnetic resonance imaging of the brain was normal. Lumbar puncture (LP) CSF analysis was done, and smears were hypercellular showing clusters along with scattered blasts displaying enlarged rounded nuclei, prominent nucleoli, fine chromatin, and scant-to-moderate cytoplasm [Figure 1]. Repeat marrow examination was negative for blast cells. There were no other systemic symptoms, and diagnosis of isolated CNS blast crisis was made. After multidisciplinary discussion, the patient received intrathecal methotrexate and therapeutic cranial irradiation 2400 cGy in 12 fractions; parallel opposed external beam radiotherapy with 6 MV photons. The decision to omit spinal radiation was taken as we expected severe cytopenia following irradiation of whole spine. The patient was offered to shift to dasatinib and for allogeneic BM transplant initially, but the patient refused since the patient was not medically insured. Repeat LP CSF cytology was negative for any blast cells.
Figure 1: Hypercellular smear showing cluster and scattered blast cells among the cerebrospinal fluid (Papanicolaou staining: ×200)

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  Discussion Top

CML is characterized by increased and unregulated growth of cells in the BM and the accumulation of these cells in the blood. Course of CML is typically chronic phase and over the several years progresses to an accelerated phase and ultimately to terminal blast crisis. In most of the patients, blastic transformation is characterized by increased blast cells in the marrow and blood, but few patients, i.e., 5%–10% of cases develop extramedullary blast crisis which may involve lymph nodes, serosal surfaces, and gastrointestinal and genitourinary system. However, CNS infiltration by blast cells is extremely rare.[2],[3] CNS involvement usually accompanies systemic involvement. However, isolated CNS blast crises are rarer and are limited to only few case reports.[3] Headache and vomiting are the common clinical manifestations for CNS relapse and require CSF evaluation as in our case. Papilledema is the most common fundus finding, and leptomeningeal enhancement is the most common imaging finding.[1]

Imatinib mesylate (STI-571) is a potent, selective BCR-ABL tyrosine kinase inhibitor. It has emerged as the treatment of choice for Philadelphia-positive CML patients in chronic phase and who are not candidates for allogeneic hematopoietic stem cell transplantation.[3],[4] It can induce hematological response in 95% of patients and major cytogenetic response in more than 60% of CML patients.[2] It has also shown activity in the accelerated and blastic phases of CML. However, the penetration of the drug and its active metabolites into CNS is poor mainly due to the increased efflux of the drug from CNS due to P-glycoprotein.[4],[5]

Systemic and intrathecal chemotherapy, radiation, and allogeneic hematopoietic stem cell transplantation are the different treatment modalities in combination for CML with CNS blast crisis.[6] Most of the reported CNS relapse cases were treated with combined intrathecal chemotherapy and craniospinal irradiation with superior treatment outcome in comparison to the intrathecal treatment alone.[1],[7] Variable combination of methotrexate, cytarabine, and dexamethasone/hydrocortisone is used as intrathecal chemotherapy. Our case was treated with both intrathecal chemotherapy and cranial irradiation.

Second-generation targeted BCR/ABL1 tyrosine kinase inhibitors, such as nilotinib and dasatinib, have an improved penetration of the blood–brain barrier. However, single cases of isolated CNS blast crises have been reported only due to paucity of data.[6],[8]

The pathogenesis of CNS leukemia is still not clear. The possible mechanisms of leukemia cells to enter the CNS are blood source diffusion, meningeal implantation, cranial BM infiltration, or LP injury.[9] Mbekeani et al. reported complete remission in a patient of CML relapsing with CNS blast crisis and bilateral optic nerve infiltration after systemic, intrathecal chemotherapy, radiation, and allogeneic hematopoietic stem cell transplantation.[10]

  Conclusion Top

The CNS may act a sanctuary site in a patient of CML on prolonged imatinib therapy as penetration is poor. Thus, there is a growing need of CNS prophylaxis in patients with CML in blast crisis even though imatinib offers complete hematological response in more than 95% of patients.

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

Kiran PK, Badarke GV, Suresh CN, Srinivas BJ, Naik R. Isolated central nervous system blast crisis in a case of chronic myeloid leukemia on dasatinib. South Asian J Cancer 2018;7:170.  Back to cited text no. 1
[PUBMED]  [Full text]  
Altintas A, Cil T, Kilinc I, Kaplan MA, Ayyildiz O. Central nervous system blastic crisis in chronic myeloid leukemia on imatinib mesylate therapy: A case report. J Neurooncol 2007;84:103-5.  Back to cited text no. 2
Rajappa S, Uppin SG, Raghunadharao D, Rao IS, Surath A. Isolated central nervous system blast crisis in chronic myeloid leukaemia. Hematol Oncol 2004;22:179-81.  Back to cited text no. 3
Peggs K, Mackinnon S. Imatinib mesylate – The new gold standard for treatment of chronic myeloid leukemia. N Engl J Med 2003;348:1048-50.  Back to cited text no. 4
Neville K, Parise RA, Thompson P, Aleksic A, Egorin MJ, Balis FM, et al. Plasma and cerebrospinal fluid pharmacokinetics of imatinib after administration to non-human primates. Clin Cancer Res 2004;10:2525-9.  Back to cited text no. 5
Jin M, Xuan C, Gao J, Han R, Xu S, Wang L, et al. Chronic myeloid leukemia extramedullary blast crisis presenting as central nervous system leukemia: A case report. Medicine (Baltimore) 2018;97:e13131.  Back to cited text no. 6
Papageorgiou SG, Pappa V, Economopoulou C, Tsirigotis P, Konsioti F, Ionnidou ED, et al. Dasatinib induces long-term remission in imatinib-resistant Philadelphia chromosome-positive acute megakaryoblastic leukemia but fails to prevent development of central nervous system progression. Leuk Res 2010;34:e254-6.  Back to cited text no. 7
Gaur S, Torabi AR, Corral J. Isolated central nervous system relapse in two patients with BCR-ABL-positive acute leukemia while receiving a next-generation tyrosine kinase inhibitor. In Vivo 2014;28:1149-53.  Back to cited text no. 8
Moazzam AA, Drappatz J, Kim RY, Kesari S. Chronic lymphocytic leukemia with central nervous system involvement: Report of two cases with a comprehensive literature review. J Neurooncol 2012;106:185-200.  Back to cited text no. 9
Mbekeani JN, Abdel Fattah M, Al Nounou RM, Chebbo W, Dogar MA. Chronic myelogenous leukemia relapse presenting with central nervous system blast crisis and bilateral optic nerve infiltration. J Neuroophthalmol 2016;36:73-7.  Back to cited text no. 10


  [Figure 1]

  [Table 1]


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