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 Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 40  |  Issue : 4  |  Page : 195-200

Demographic, clinical, and hematologic characteristics of patients with chronic myeloid leukemia in Upper Egypt: association with treatment responses


1 Department of Internal Medicine, Hematology and BMT Unit, Assiut University Hospital, Faculty of Medicine, Assiut University, Assiut, Egypt ; College of Applied Medical Sciences at Al Dawadmi, Shaqra University, Shaqra, Riyadh, Saudi Arabia
2 Department of Medical Oncology, South Egypt Cancer Institute, Assiut, Egypt ; Deparment of Hematology/Oncology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia

Date of Submission24-Apr-2015
Date of Acceptance23-Jun-2015
Date of Web Publication23-Nov-2015

Correspondence Address:
Safaa A. A. Khaled
Department of Internal Medicine, Hematology and BMT Unit, Assiut University Hospital, Assiut 71111, Egypt

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-1067.170221

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  Abstract 

Background and objectives Chronic myeloid leukemia (CML) is a relatively indolent hematologic malignancy that carries poor prognosis if left untreated. With the recent advances in treatment options for CML, therapy could be tailored to each patient based on patient and/or disease characteristics. This research aimed to study the characteristics of patients with CML in Upper Egypt and to investigate their influence on various therapeutic responses.
Patients and methods A retrospective study was conducted at the Hematology Unit of Assiut University Hospital and South Egypt Cancer Institute. The demographic, clinical, hematologic, and follow-up data of patients with CML were extracted from hospital records at both Assiut University Hospital and South Egypt Cancer Institute during the period from January 2007 to December 2012, representing a total of 180 patients. Records with incomplete data or unavailable follow-up were excluded from the study.
Results and conclusion The median age of participants was 42 years, and the male-to-female ratio was 1 : 1.7. The Eastern Cooperative Oncology Group Performance Status was the most important effector of both hematologic and therapeutic responses (P = 0.000), followed by the phase of the disease (P = 0.000 and 0.017, respectively), and lastly the Philadelphia chromosome (P = 0.07 and 0.000, respectively). Moreover, leukocytosis was associated with poor hematologic and cytogenetic responses (r = 0.19, P = 0.000; r = −0.16, P = 0.05). A small proportion of patients achieved complete hematologic and cytogenetic responses (45 and 52%, respectively). These novel findings may reflect a trend of young age, female-predominant CML in Upper Egypt and could be attributed to the ethnic and socioeconomic differences of our patients compared with those in similar studies.

Keywords: chronic myeloid leukemia, demographics, Upper Egypt


How to cite this article:
Khaled SA, Abd El Aziz NM. Demographic, clinical, and hematologic characteristics of patients with chronic myeloid leukemia in Upper Egypt: association with treatment responses. Egypt J Haematol 2015;40:195-200

How to cite this URL:
Khaled SA, Abd El Aziz NM. Demographic, clinical, and hematologic characteristics of patients with chronic myeloid leukemia in Upper Egypt: association with treatment responses. Egypt J Haematol [serial online] 2015 [cited 2019 Dec 8];40:195-200. Available from: http://www.ehj.eg.net/text.asp?2015/40/4/195/170221


  Introduction Top


Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder that possesses a characteristic cytogenetic profile [1],[2] . Treatment of CML went through a series of discoveries that began with arsenic and ended in 1998 with the marvelous discovery of tyrosine kinase inhibitor, which is a targeted therapeutic agent that markedly changed the survival of CML patients [3],[4] .

The first reported case of leukemia was that of a 63-year-old man, with a splenomegaly 20 times normal and pus in his blood. Since this description, further studies showed a median age of CML patient at diagnosis of 55-60 years, and the male population was predominantly affected compared with the female population. Clinically, a CML patient is characterized by huge splenomegaly associated hematologically with marked leukocytosis, particularly in the chronic phase of the disease [5] . Women were found to have better overall survival with interferon therapy [6] . Studies have also shown that the socioeconomic state of the patients affects their treatment response, particularly after the introduction of the highly priced tyrosine kinase inhibitors [7] . Most of these studies were based on Western Cancer Registry information. Few recent studies conducted in East Asia and Middle Eastern countries showed little or no change compared with the findings of the western ones [8],[9] . A recent study in the Nile delta and a report in Aswan emphasized on incidence rates and the pattern of incident cancer cases in an attempt to give clues to the burden and pattern of cancer in Egypt [10] . This study was conducted in Upper Egypt to investigate the demographic, clinical, and hematologic characteristics of CML patients in Upper Egypt. Another objective was to find out the diagnostic and prognostic effects of these characteristics by correlating patient data with various treatment responses regardless of the stage of the disease or the type of treatment.


  Patients and methods Top


Patient and data collection

We retrospectively collected the demographic, clinical, and hematologic data of CML patients who had been referred to the Hematology Unit of Internal Medicine Department at Assiut University Hospital and to South Egypt Cancer Institute, during the period from January 2007 to December 2012. Data were collected by reviewing patients' records and registry; both computer-based and handwritten patients' records were reviewed. Records with incomplete data were omitted from the study.

The demographic data included patient's age, sex, residence, occupation, and social status. Clinically, symptoms and signs, including the Eastern Cooperative Oncology Group performance status, splenomegaly, hepatomegaly, and lymphadenopathy, were recorded. As regards the hematologic data, they included total leukocytic count, hemoglobin, and platelet counts. In addition, the CML phase and the Philadelphia (Ph) for each case were analyzed; however, for some cases the Ph was not analyzed.

Follow-up data

Each file was reviewed for a follow-up period of 3 months or more to record the treatment received and the treatment responses. For some patients both hematological and cytogenetic responses were available and for others only the hematologic response was achieved. This was due to the unavailability of molecular testing during the period from 2007 to 2009, particularly at Assiut University Hospital. Files with less than 3-month follow-up were not included in the study.

Treatments and definition of responses

Patients received either hydoxyurea or Gleevec as first-line or second-line therapy. A small group of patients was treated with other therapies, mainly α-interferon. Treatment responses were assessed after 3 months of therapy. Complete hematologic response (CHR) was defined as a total leukocytic count less than 10 × 10 9 /l without immature granulocytes, with less than 5% basophils, and a platelet count less than 450 × 10 9 /l. Cytogenetic response was evaluated on the basis of fluorescence in-situ hybridization analysis and categorized as complete (CCyR) (absence of Ph-positive cells), partial (1-35% Ph-positive cells), minor (36-65% Ph-positive cells), minimal (66-95% Ph-positive cells), or no response (>95% Ph-positive cells) [11] . Molecular responses were unavailable for most of our patients and thus were not included in analyses.

Statistical methods

The frequency tables and standard descriptive statistics (mean, median, minimum, and maximum) were used to summarize patient characteristics. Association between patients' characteristics and the various therapeutic responses was assessed with the χ2 -test.

Correlations of patients' data and therapeutic responses were assessed using Spearman's correlation test. Association between quantitative variables and the obtained therapeutic responses was analyzed with Pearson's correlation.

Level of statistical significance was set at 0.05. Analyses were performed using statistical software SPSS, 0.17 (SPSS Inc., Chicago, Illinois, USA).

Ethical considerations

The study design, method, and objectives were consistent with the World Medical Association (WMA) Declaration of Helsinki, 2013. The study protocol was approved by the University of Assiut, Faculty of Medicine Research ethical committee.


  Results Top


Patients' characteristics

A total of 180 CML patients were enrolled in the study; their ages ranged from 16 to 80 years, with a median age of 42 years. An overall 57.2% of them were female, with a male-to-female ratio of 1 : 1.7. An overall 78% of them were in the chronic phase and 57% were Ph-positive. [Table 1] summarizes the demographic, clinical, and hematologic characteristics of the study group, the treatment they received, and the various therapeutic responses.
Table 1 Demographic, clinical, and hematologic characteristics of the study group (N = 180)


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Associations between patients' characteristics and the obtained therapeutic responses

Overall, the current study showed no sex, age, or social-based differences in therapeutic responses. In contrast, a significantly higher proportion of patients with restricted strenuous activity and/or with chronic phase diseases achieved both CHR and CCyR (P = 0.001 and 0.017, respectively). Ph positivity was associated with greater CCyR (P = 0.001). These relations are presented in [Table 2] and [Table 3].
Table 2 Crosstabulation results of patient characteristics and hematologic therapeutic response


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Table 3 Cross tabulation results of patient characteristics and cytogenetic therapeutic response


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Effect of patients' hematologic parameters and the obtained therapeutic responses

The relationship between patients' hematologic parameters and both the HR and CyR was analyzed. The obtained results showed a significant negative correlation between TLC and CyR (r = -0.16, P = 0.05). Also a significant negative correlation between Hb and both HR and CyR was observed (r = -0.269 and -0.25 respectively, P = 0.00). As depicted in [Table 4].
Table 4 Correlations between patient characteristics and the hematologic and cytogenetic therapeutic responses


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Relationship between the type of CML treatment and the various therapeutic responses

All patients included in the study were treated and assessments of their hematologic and cytogenetic responses were carried out over 3 months thereafter. An overall 50.6% of patients received hydroxyurea as first-line therapy and 37.2% received Gleevec either as first-line or second-line therapy. Only 12.2% of patients received other therapies, mainly interferon alpha. Despite the curative effect of the hematopoietic stem cell transplantation (HSCT), none of our patients had undergone HSCT. This was due to the unavailability of suitable donors and the decreased needs to perform HSCT after the introduction of the tyrosine kinase inhibitors. An overall 71.6 and 67.2% of patients treated with Gleevec achieved complete hematologic and cytogenetic responses, respectively. For those treated with hydoxyurea, only 34.1 and 31.9% reached to complete therapeutic responses. Failure of hematologic and cytogenetic responses was observed in 6 and 13.4%, and 14.3 and 18.7% of patients treated with Gleevec and hydoxyurea, respectively. Disease progression was noted in 21.7% of the study group. [Figure 1] and [Figure 2] illustrate the influence of the type of treatment on the obtained therapeutic responses.
Figure 1 Relationship between the type of chronic myeloid leukemia treatment and the obtained hematologic response

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Figure 2 Relationship between the type of chronic myeloid leukemia treatment and the obtained cytogenetic response

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  Discussion Top


CML is a chronic myeloproliferative disorder that ranges clinically from a quiescent to rapidly fatal disease [12] . This study analyzed the demographic, clinical, and hematologic characteristics of CML patients in Upper Egypt. The associations between these characteristics and the various therapeutic responses were also investigated. The study included 180 CML patients who were originally from Al-Menia, Assiut, Sohag, Qena, and Aswan governorates of Upper Egypt. The study revealed lower median age of CML patients and higher affection of female patients and rural-resident patients, compared with that reported in other studies in other eastern and western countries [8],[9],[10] .

Consistent with other studies, the vast majorities of our patients were presented with huge splenomegaly, chronic phase, and were Ph-positive [13] . Moreover, adverse hematological features such as leukocytosis and anemia were identified in a significant proportion of the study group [14] .

Unlike other studies, most of our patients failed to achieve CHR at 3 months. This could be attributed to tyrosine kinase inhibitor being the main treatment [15] , unlike the current study in which different treatment methods were used.

In this study both the hematologic and cytogenetic responses of patients revealed the superior efficacy of Gleevec compared with other treatment modalities. These responses were similar to those observed by Kantarjian et al. [16] . However, the current study showed higher disease progression and response failure in those treated with Gleevec. This could be attributed to treatment interruption of the highly priced Gleevec therapy. Another major cause of treatment interruption is development of adverse events. This explanation is supported by the work of others who demonstrated that treatment interruption leads to loss of the gained therapeutic responses and even to disease progression [17],[18],[19] .


  Conclusion Top


Our results revealed a trend of younger age, female-predominant CML and that age or sex does not influence therapeutic responses. Moreover, a smaller proportion of patients achieved complete therapeutic responses. These results could be possibly due to ethnic and socioeconomic effects.

Acknowledgements

The authors thank Professor Yousseryia A. Ahmed and Professor Esam A.S. ElBieh - Internal Medicine Department, Hematology and BMT Unit, Assiut University Hospital, Assiut, Egypt - for their continuous scientific guidance.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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