Molecular Response to Treatment of Chronic Myeloid Leukemia at University Teaching Hospital of Kigali, Rwanda: One-Arm Open Label Prospective Observational Study

Abstract

Background

Chronic myeloid leukemia (CML) is among most common chronic hematological neoplasms marked by proliferation of granulocytes. Since 2001, the introduction of tyrosine kinase inhibitors (TKI), especially imatinib, the outcomes for patients with CML has improved significantly, and life expectancy is now almost the same as that of general population in developed countries. However, this is not the case in the developing world owing to the limited access to TKI. In Rwanda only imatinib is available and molecular response assessment is limited. This study describes the molecular responses of patients with CML treated with imatinib in Rwanda.

Methods

This one-arm, open-label, prospective cohort study recruited 31 patients with CML who had been on imatinib for ≥ three months. Patients were followed-up for 12 months. Clinical features and laboratory results at the time of diagnosis were retrieved from hospitals’ records. Clinical re-assessment, full blood count, and BCR::ABL1 testing were done at the time of recruitment. Data analysis was performed using SPSS 28.

Results

Using European LeukemiaNet BCR::ABL1 thresholds depending on time on imatinib; optimal, warning and failure (=resistance to imatinib) response categories were found in 38.7%; 16.1% and 45.2% respectively. The 12-month survival rate was 93.5% (n=29/31), all deaths (2/31) occurred in treatment failure group. Patients with late presentation (white blood cell counts >100x10⁹/L and massive splenomegaly) at diagnosis and/or poor adherence to imatinib measured by the Morisky Medication Adherence Scale (MMAS-8), had a poor molecular response to imatinib.

Conclusion

Although the 1-year survival rate was good for patients with CML treated with imatinib, the molecular response was generally poor. This may be due to late presentation and poor adherence to imatinib which needs further investigations. To improve the survival of patients with CML in Rwanda, access to all available lines of TKI and better follow-up should be considered.

Introduction

Chronic Myeloid Leukemia (CML) is one of the most common myeloproliferative neoplasms worldwide,¹ with no exception to Rwanda.² It is a clonal disorder that originates from pluripotent hematopoietic stem cells following a chromosomal translocation t(9;22)(q34.1; q11.2), which results in the formation of the Philadelphia chromosome that is chromosome 22 containing the fusion gene BCR::ABL1 and is a hallmark of the disease^3–6 It affects granulocytes, which are the major proliferative components.⁷ Predisposing factors for CML are largely unknown, and unlike other myeloproliferative neoplasms, there is a slight, if any, inherited predisposition.

CML is a rare disease, with an incidence of 0.7–2 cases per 100,000 people per year^5,8,9 and a male predominance.^5,10,11 However, there are limited data on the incidence or prevalence of CML in most African countries, especially in Rwanda, owing to the lack of sufficient studies targeting CML.¹²

The diagnosis of CML requires a full blood picture that shows leukocytosis and morphology of the peripheral blood film, bone marrow aspiration, and trephine biopsy, which show features of increased proliferation of myeloid cells.^6,13 The presence of Philadelphia chromosome is necessary for the diagnosis of CML.^4,13 It can be shown either by Fluorescence in situ Hybridization (FISH), which confirms t(9;22)(q34.1;q11.2), or by Polymerase Chain Reaction (PCR), including quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR), which shows transcripts of the chimeric fusion gene BCR::ABL1.^4,13 The latter method can detect one cell with feature of CML in 100 thousand to 1 million normal cells.^14–16 CML has three phases: chronic, accelerated, and blast crisis phase. Regarding the microscopic morphology of the bone marrow, the chronic phase shows a blast count of ≤10%, the accelerated phase of ≥10% but <20%, and the blasts crisis phase of a blasts count of ≥20% that behaves like acute leukemia.^17,18 In the developed world, most patients present in the chronic phase without symptoms and are identified by leukocytosis during regular checkups. However, in the developing world, including Rwanda, most patients present with symptoms of anemia, defined by generalized body weakness, headaches, and dizziness, which sometimes require blood transfusion, and almost 100% have splenomegaly.^{6,10,13,14,19,20}

Drugs for the treatment of CML include imatinib, which was invented in the late 1990s by the oncologist Brian Druker of Oregon Health and Science University. In 2001, the United States Food and Drug Administration (FDA) approved its medical use as a first-line treatment for CML in both adult and pediatric patients.^21–23 Since the introduction of imatinib and other Tyrosine Kinase Inhibitors (TKIs) in the market, CML management has been revolutionized to the extent that CML patients who continue to respond to imatinib have the same or almost the same life expectancy as the general population.^24–27

Rwanda has three centers able to provide the diagnosis and treatment of CML. However, no single center can provide the full package for the management of this disease: a patient may receive provisional diagnosis at one center and then referred to another center for confirmation of diagnosis and or treatment. In addition, patients in Rwanda only have access to imatinib because no other TKIs lines are available in the country and monitoring of response using RT-PCR is limited and available in only two hospitals. Imatinib has been available in Rwanda since 2011, and patients diagnosed thereafter have benefited from this drug free of charge thanks to the sponsorship of Glivec International’s Patient Assistance Program (GIPAP), which was established by Novartis Pharma AG and implemented by a Non-Governmental Organization (NGO) called The Max Foundation.² Therefore, in Rwanda, all patients were administered imatinib without considering their phases, or whether they had transformed or not. This has made the overall survival of patients with CML in Rwanda different from that of patients in the developed world. This is because in case patients in Rwanda were found to have a poor response to imatinib, they had no alternative options for treatment as alternative TKI are not available in the country.²⁸ Other available generations of TKI approved for CML and which have been on the market for long period of time include dasatinib, bosutinib, nilotunib, ponatinib specific for treating those with famous T315I mutation. TKI currently coming on the market is asciminib; all of those are superior to imatinib and have shown great response to those with resistance to imatinib.

For Rwandan patients with CML, data on the clinical presentation, diagnosis, management, and follow-up—including adherence to treatment using appropriate tools such as Morisky Medication Adherence Scale (MMAS-8)²⁹—are scarce and patients claim insufficiency of care. This study examined the clinical presentation, survival risk factors using Sokal score³⁰ and investigated the molecular responses and outcomes of patients with CML treated with imatinib at the University Teaching Hospital of Kigali (CHUK). The study reported a higher survival rate (93.5%) at 12-month of follow-up despite a higher rate of treatment failure (45.2%) in patients with CML treated with imatinib in Rwanda.

Material and Methods

Study Population

We conducted a hospital-based, one-arm, open-label prospective observational study that recruited patients aged at least 18 years with a diagnosis of CML who had been on imatinib treatment for at least 3 months (90 days) before recruitment. Patients were recruited from May 2022 and followed up until April 2023, with 12 months of follow-up. Our study participants received imatinib in different hospitals, including Butaro Cancer Center of Excellence (BCCOE), Rwinkwavu Hospital, and Rwanda Military Teaching Hospitals (RMTH).

Data Collection Tools

A well-structured questionnaire with direct interviews with patients was used to obtain information such as age, sex, date of diagnosis, history of transfusion before and after diagnosis, date of starting medications, and current symptoms. The MMAS-8²⁹ was used to collect information related on adherence to treatment. The patients were examined to obtain their current physical examination findings. Clinical presentation and laboratory findings at the time of diagnosis were retrieved from the hospital records.

Laboratory Tests

For every participant, two tubes of 4.5 mL of venous blood were withdrawn in EDTA tubes. One sample was used for the full blood count, whereas the second sample was used for qRT-PCR to quantify BCR::ABL1 transcripts. Blood sampling and laboratory analyses were performed at CHUK. Samples for qRT-PCR were stored in fridge at 2–8°c while waiting analysis. However, the laboratory tests were performed within 24h. The Xpert BCR-ABL Ultra Kit (Cepheid, 904 Caribbean Drive, Sunnyvale, CA 94089, USA) was used to detect BCR::ABL1 copies, and the tests were run on a GeneXpert machine (Cepheid) according to the manufacturer guidelines. Results were interpreted following the instruction available in the Instruction for Use of The Xpert ^® BCR-ABL Ultra Kit (Cepheid ^®).³¹

Assessment for Molecular Response, Adherence to Imatinib and Survival Risk

We assessed the molecular response to imatinib using the quantitative measurement of BCR::ABL1/ABL1 as reported in the European LeukemiaNet (ELN) recommendations, and the response was classified as optimal, warning, or failure³⁰ depending on the level of BCR::ABL1 as described in Table 1.

Table 1.

Criteria for Assessment of Molecular Response to Imatinib of Patients with CML at Different Time of Treatment³⁰

Time	Optimal	Warning	Failure
3 months	BCR-ABL1 ≤ 10%	BCR-ABL1 > 10%	>10% if confirmed within 1–3 months
6 months	BCR-ABL1<1%	BCR-ABL1 >1–10%	BCR-ABL1 >10%
12 months	BCR-ABL1 ≤ 0.1%	BCR-ABL1> 0.1–1%	BCR-ABL1 > 1%
Then, and at any time	BCR-ABL1 ≤ 0.1%	BCR-ABL1 >0.1–1% Or loss of ≤ 0.1%	>1%, resistance mutations, high-risk ACA

Abbreviation: ACA, Additional chromosomal abnormalities.

The adherence to imatinib was assessed using MMAS-8 and results were classified in three categories: a score of <6 denotes low adherence, a score of 6 to <8 corresponds to medium adherence, and a score = 8 denotes high adherence.²⁹

The Sokal score, that use age, spleen size, platelet count, and percentage of myeloblasts at the time of diagnosis, was employed for survival risk assessment. Patients are classified into three groups: low-risk (score of <0.8), intermediate risk (score of 0.8–1.2) and high risk (score of >1.2).³⁰

Statistical Analysis

Data were analyzed using SPSS version 28. Descriptive statistics were used to summarize the sociodemographic data and clinical characteristics of the participants. The Kaplan–Meier test was used to calculate survival time, and the Log rank test was used to estimate the significance of survival among ELN molecular response categories.

Ethical Considerations

Ethical approval was obtained from the Institutional Review Board of the University of Rwanda (Approval Notice: No. 329/CMHS IRB/2021) and permission to conduct the study was obtained from the University Teaching Hospital of Kigali (Review Approval Notice Ref.:EC/CHUK/002/2022). Written informed consent was obtained from all patients before recruitment and all procedures were conducted in accordance with the Declaration of Helsinki.

Results

Demographic and Baseline Characteristics

We analyzed data from 31 patients. The majority (48.4%, 15/31) were enrolled from the Rwinkwavu Hospital, one of the three hospitals in Rwanda that can provide imatinib. The male-to-female ratio was approximately 1:1 (16 males, 15 females). Most patients had been on imatinib for 1–5 years (32.3%, 10/31). More details on demographic and baseline clinical data are summarized in Table 2.

Table 2.

Demographic and Baseline Characteristics of Patients with CML at CHUK

Characteristic	Number of Patients (n=31, Median Age=40 Years, Range=18–71 Years)	Percentage (%)
Hospital administering Imatinib (n=31)
Rwinkwavu	15	48.4
RMTH	12	38.7
BCCOE	4	12.9
Gender (n=31)
Male	16	51.6
Female	15	48.4
Residence (n=31)
Kigali city	13	41.9
Eastern province	11	35.5
Southern province	6	19.4
Foreigner	1	3.2
Marital status (n=31)
Married/Co-habiting	17	54.8
Single	11	35.5
Divorced/separated	2	2.5
Widow/widower	1	3.2
Time on imatinib (n=31)
3–<6months	2	6.5
6–<12 months	1	3.2
1 year	2	6.5
1–5 years	10	32.2
5–10 years	9	29.0
>10 years	7	22.6
Education (n=31)
No formal education	4	12.9
Primary school	9	29.0
Secondary school	8	25.8
University and above	10	32.3
Living arrangement (n=31)
Living alone	5	16.1
Living with someone	26	83.9
Employment (n=31)
Self-employed (business)	10	32.3
Civil servants	7	22.6
Un-employed	7	22.6
Peasants/farmers	6	19.3
Students	1	3.2

Abbreviations: BCCOE, Butaro Cancer Center of Excellence; RMTH, Rwanda Military Teaching Hospital.

Clinical Presentation at the Time of Diagnosis

Most patients presented with symptoms of anemia (90.3%, 28/31) and splenomegaly (87.1%, 27/31). Leukostasis symptoms, which were mostly characterized by blurred vision and reduced hearing capacity, were present in 25.8% of patients. The median WBC count and hemoglobin level at diagnosis were 218 × 10³/μL and 9.5 g/dL, respectively. Bone marrow aspiration and biopsy were performed in only 45.2% (14/31) of patients. All patients who underwent a bone marrow test were in the chronic phase. Based on Sokal score,³⁰ a total of 58.1% (18/31) of patients were in high risk, whereas only 3.2% (1/31) were in low-risk category at the time of diagnosis; details are provided in Table 3.

Table 3.

Clinical and Laboratory Presentations of Patients at the Time of CML Diagnosis

Categories & Parameters	Number of Patients (n=31)	Percentages (%)	Median (Range)
Baseline hematological findings
WBC, ×103/µL			218 (27–500)
Platelets, ×109/L			300 (91–789)
Hemoglobin, g/dL			9.5 (6–17)
Baseline molecular findings
BCR::ABL1 positive	31	100
Blasts in BM aspiration <10%	14	45.2
Symptoms and signs at diagnosis
Symptoms of anemia	28	90.3
Bleeding	7	22.6
Splenomegaly	27	87.1
Hepatomegaly	11	35.5
Symptoms of leukostasis	8	25.8
Bone marrow aspiration at diagnosis
Done	14	45.2
Not done	17	54.8
Comorbidities at time of diagnosis
Comorbidities (HIV, HTN, DM)	2	6.5
No comorbidity	29	93.5
Sokal risk score
Low risk	1	3.2
Intermediate risk	12	38.7
High risk	18	58.1
Transfusion history
Prior to imatinib (pRBCs, 1–3 units)	10	32.3
No prior transfusion	21	67.7
After imatinib (pRBCs, platelets, or both)	4	12.9
No transfusion after imatinib	27	87.1

Abbreviations: WBC, white blood cells; HIV, Human Immunodeficiency Virus; HTN, hypertension; DM, Diabetes mellitus; pRBCs, packed red blood cells.

Treatment for CML, Related Side Effects, and Molecular Response to Treatment

All patients were administered imatinib. This was regardless of how long they had been taking it. It was also regardless of how they had responded to it. Most patients (45.2%, 14/31) had been receiving imatinib for >12 months. Our patients showed good adherence to treatment, with 51.1% scoring high, 32.3% medium, and 16.1% low adherence. The side effects of imatinib were reported in 74.2% (23/31) of patients. The most common side effects were nausea and vomiting, which were present in 32.3% (10/31) of patients. No patient had to change the TKI type owing to the severity of the side effects; however, 43.5% experienced dose interruption, which was defined as reducing the dose or withholding it for a period of time. Although some patients have been receiving imatinib for a long time, their molecular response was low. Only 38.7% of patients had an optimal response to imatinib, 45.2% experienced treatment failure, and 16.1% had a warning status; details are illustrated in Table 4.

Table 4.

Treatment of CML, Molecular Response to Treatment and Side Effects of Treatment

Characteristic	Number of Patients (n)	Percentage (%)
Duration on TKI at Recruitment (n=31)
3 months	2	6.5
6 months	2	6.5
12 months	13	41.8
>12 months	14	45.2
MMAS-8 adherence scale (n=31)
Low adherence	5	16.1
Medium adherence	10	32.3
High adherence	16	51.6
Molecular response (n=31)
Optimal	12	38.7
Warning	5	16.1
Failure	14	45.2
Side effects of imatinib (n=31)
Yes	23	74.2
No	8	25.8
Types of side effects on imatinib (n=31)
Nausea/vomiting	10	32.3
Diarrhea	2	6.5
Muscle cramps/pain	8	25.8
Oedema	9	29.0
Cytopenia	8	25.8
Skin rash	5	16.1
Fever	2	6.5
Weight gain	5	16.1
Hemorrhage	2	6.5
Duration of side effects (n=21)
< 1 month	3	9.7
1–3 months	10	32.3
3–12 months	3	9.7
>12 months	5	16.1
Dose interruption because of side effects (n=31)
Yes	11	35.5
No	20	64.5

Abbreviations: MMAS-8, Morisky Medication Adherence Scale-8; TKI, Tyrosine Kinase Inhibitors.

Overall Survival

Patients were followed-up for 12 months from the time of recruitment. After 12 months, the patients or their relatives were contacted to determine if they were still alive. Two patients died during the follow-up period (one died five months after recruitment and the other one after nine months after recruitment). Both were in the treatment failure category at the time of assessment and died from CML transformation to acute leukemia, which is not treatable in Rwanda. Therefore, at the end of the follow-up period, the overall survival rate of patients with CML at CHUK was 93.5%. Kaplan Meier Survival analysis rates according to ELN molecular response are illustrated in Figure 1. Patients in the warning category and those with an optimal response to imatinib had a 100% survival rate during the 12-month follow-up period, whereas those in the treatment failure category had an 85.7% survival rate. However, the p value for this difference was 0.28, which was not statistically significant and may be due to the short follow-up period.

Figure 1.

Kaplan Meier Survival analysis rates according to ELN molecular response. There is no death recorded in 12-month period of follow up for patient in optimal and warning category. However, 2 deaths occurred in a group of patients in failure category. However, this data should be interpreted descriptively and with caution due to the fact that our cohort is very small and with a short follow-up period.

Analysis of Risk Factors and White Blood Cells Count in the Perspective of Molecular Response Levels

Table 5 provides an overview of the frequency of different risk factors according to molecular response category. In summary, most 87.1% (27/31) of patients had splenomegaly at the time of diagnosis. Accordingly, 58.1% (18/31) were in high-risk category. The median of white blood cell counts at diagnosis tended to be high as the level of response to treatment worsened, as illustrated in Figure 2.

Table 5.

Frequency of Different Risk Factors According to Molecular Response Categories

Characteristic	Optimal n (%)	Warning n (%)	Failure n (%)	Total n (%)
Splenomegaly
Yes	10 (37.0)	5 (18.5)	12 (44.4)	27 (87.109)
No	2 (50.0)	0 (0.0)	2 (50.0)	4 (12.9)
Sokal Score
Low risk	0 (0.0)	0 (0.0)	1 (100)	1 (3.2)
Intermediate	6 (50.0)	1 (8.3)	5 (41.6)	12 (38.7)
High risk,	6 (33.3)	4 (22.2)	8 (44.5)	18 (58.1)
MMAS-8
High adherence	5 (41.7)	3 (60.0)	8 (57.1)	16 (51.6)
Medium Adherence	6 (50.0)	2 (40.0)	2 (14.3)	10 (32.3)
Low Adherence	1 (8.3)	0 (0.0)	4 (28.6)	5 (16.1)

Abbreviations: MMAS-8: MMAS-8: Morisky Medication Adherence Scale-8.

Figure 2.

White blood cells count at diagnosis. The median of white blood cell counts at diagnosis tended to be high as the level of response to treatment worsen.

Discussion

This single-arm, open-label, prospective cohort study, describes the clinical presentation, modality of treatment, rate and type of side effects, the molecular response to imatinib and one-year survival rates for patients with CML at CHUK.

Clinical Presentation, Modality of Treatment and Side Effects

In this study, the median age of participants was 40 years with an age range of 18–71 years. Morgan et al² reported a median age of 34 years; Nasser et al¹⁴ reported a median age of 45 years (range, 18–86), while Petzer et al³² reported a median age of 56 years (range, 18–90). The male-to-female ratio was approximately 1:1 which is similar to findings reported by dos Reis et al.³³ Previous study done in Rwanda^2,28 reported a male predominance and most studies confirm a male predominance in patients with CML.^11,14,32 Most patients (32.3%, 10/31) had been on imatinib for 1–5 years. This is because no alternative TKI are available in Rwanda. In this context, patients who are not responding to imatinib as well as those who may need to changes imatinib because of side effects have no choice. The lack of alternative TKI may contribute to poor treatment responses and low adherence to treatment both of which may contribute to poor prognosis. Of note is that in developed countries, different kinds of TKI are now available for treatment of patients with CML.³⁴ The availability of various drugs has contributed to better treatment adherence and quick response to therapy.¹³ The side effects of imatinib were reported in 74.2% of patients. Faye et al¹¹ reported a rate of 60% of participants experiencing side effects, Nasser et al reported side effects of imatinib in 83.5%,¹⁴ while Gatea et al reported that side effects occurred in 82.6% patients with good adherence to imatinib.³⁵ The most common side effects were nausea and vomiting, which were present in 32.3% of patients. Previous studies also reported that gastrointestinal signs and symptoms are among the most common side effects of imatinib treatment.^8,14,35 Despite presence of side effects of imatinib in some patient, no patient had the opportunity to change the TKI type as there was no alternative treatment as a consequence, 43.5% experienced dose interruption. Dose interruption due to side effect was also reported in prior studies.^14,35

Anemia was present in 90.3%, splenomegaly in 87.1%, hepatomegaly in 35.5% and symptoms of leukocytosis in 25.8%. These signs and symptoms are reported in different studies with variation in their rate of occurrence.^{8–11,14,19,36} Bone marrow aspiration and biopsy were performed in only 45.2% (14/31) of patients despite that bone marrow aspirate is a recommended exam for morphological assessment in cases with a diagnosis of CML to differentiate chronic phase from accelerated and blastic phases.³⁰ All patients who underwent a bone marrow test were in the chronic phase. Prior reports confirm that most of patients consult when they are in chronic phase.^13,14,33,37 The assessment of survival risk found that a total of 58.1% of patients were in high risk, 38.7% in intermediate risk whereas only 3.2% were in low-risk category at the time of diagnosis. In Tanzania, a neighbor country to Rwanda, Nasser et al reported rates of 41.0%, 49.0% and 10.0% for high, intermediate and low risk, respectively.¹⁴ However, the sokal risk reported by Scalzulli et al are far different from the findings of the current study: 4% for high risk, 33% for intermediate risk and 63% for low-risk group.³⁸

Molecular Response of Patients with CML on Imatinib

In this study, treatment failure was observed in 45.2% (14/31) of patients. Furthermore, 16.1% (5/31) of the patients were in the warning zone, whereas only 38.7% (12/31) exhibited an optimal response. Most of the patients had been receiving treatment for >12 months. Similar findings have been documented by Nasser et al in Tanzania, who revealed that patients undergoing treatment for a period exceeding twelve months exhibited a diminished response rate¹⁴. Meta-analysis was conducted to compare the effectiveness of imatinib, nilotinib, and dasatinib. A study conducted by Signorovitch et al revealed that patients treated with imatinib exhibited a major molecular response of 44.8% after one year of follow-up, whereas those treated with nilotinib demonstrated a response of 97%.³⁹ However, a significant discrepancy exists between the data reported by studies conducted in developed countries, where a substantial molecular response was observed in an imatinib study. A study by Andreas L. Petzer et al demonstrated that a major molecular response was attained in 77.3% of cases in Austria;³² similarly, Gianantonio et al reported a major molecular response among 79% of patients.⁴⁰

The low response rate of CML patients to imatinib in Rwanda may be due to two factors. First, patients present late to medical care and second, they demonstrate poor adherence to treatment. The presentation was made at a later stage, and all patients had symptoms. The baseline assessment revealed the presence of splenomegaly and elevated white blood cell counts in a significant number of patients. Conversely, low adherence to imatinib was significantly seen in patients with treatment failure. Roosevelt et al reported analogous findings, indicating that patients with high adherence to imatinib exhibited a superior response to treatment.³³

Overall Survival

In the present study, the overall survival rate of patients with CML who were administered imatinib for a minimum of three months and followed for a period of 12 months was 93.6%. The survival rate was 100% for the patients in the optimal response and warning categories. The overall survival rate of the patients who experienced treatment failure was 85.7%. Lower overall survival rates have been observed in both developing and developed countries. Nasser et al reported an overall survival rate of 81.7% for patients with CML in Tanzania over a 22-month follow-up period,¹⁴ and almost the same overall survival rate was reported by Sacha et al,²³ who reported 85% overall survival for patients receiving imatinib in Poland. Hagop et al in Texas reported that, after an eight-year period of observation, the overall survival rate of patients treated with imatinib was 75%.³⁷ The elevated overall survival rate documented in this study, notwithstanding the considerable incidence of treatment failure, may be ascribed to the relatively brief follow-up period.

Limitations of Our Study

This study has several limitations. First, the one-arm, open-label design without a comparator group restricts the ability to draw causal inferences and compare results with those of other tyrosine kinase inhibitors. Second, the small sample size from a single center reduced the statistical power of the findings and their generalizability. Third, the relatively short follow-up period may have overestimated the overall survival and did not allow to estimate late treatment failures. Finally, the limited baseline molecular and cytogenetic risk stratification may have confounded the assessment of the treatment response.

Conclusion

This study demonstrated high overall survival rates after 12 months of follow-up among CML patients treated with imatinib at CHUK, despite a significant number of patients experiencing suboptimal molecular responses or treatment failures. Late presentation and poor adherence were key factors associated with an inferior response. Imatinib was generally well tolerated; however, frequent dose interruptions may have contributed to its reduced effectiveness. The relatively short follow-up period likely explains the discrepancy between the survival and molecular outcomes. Furthermore, the findings highlight the difficulties in early diagnosis, follow-up and management of CML cases, especially due to lack of alternative TKI. Therefore, to improve the survival of patients with CML in Rwanda, it is very important to enhance and improve earlier diagnosis, adherence support, access to molecular monitoring and advocacy to avail alternative second- and third-generation TKI that offer additional options for patients who may develop resistance or intolerance to imatinib. In addition, larger multicenter studies with longer follow-up periods are necessary to better define long-term outcomes in Rwanda.

Funding Statement

This study was funded by the University Teaching Hospital of Kigali, Research Grant Number RC/CHUK/005/2021.

Use of Generative Artificial Intelligence

In this study, we used generative artificial intelligence (AI) for the limited/few paragraphs. The AI used was Deepl.com (DeepL Write, a web-based, free-of-charge version) and was used for English editing only.

Abbreviations

CHUK, University Teaching Hospital of Kigali; CML, Chronic Myeloid Leukemia; EDTA, Etheylene di-amine tetra acetic acid; ELN, European LeukemiaNet; FDA, Food and Drug Administration; FISH, Fluorescence in Situ Hybridization; GIPAP, Glivec International’s Patient Assistance Program; MMAS-8, Morisky Medication Adherence Scale; NGO, Non-Governmental Organization; PCR, Polymerase Chain Reaction; qRT-PCR, Quantitative Reverse Transcriptase Polymerase Chain Reaction; RMTH, Rwanda Military Teaching Hospital; SPSS, Statistical Package for the Social Sciences; STATA, South Texas Art Therapy Association; TKI, Tyrosine Kinase Inhibitors; WBC, White Blood Cells.

Data Sharing Statement

Dataset is available on request from the corresponding author.

Ethics Approval and Consent to Participate

This study was approved by the Institutional Review Board of the College of Medicine and Health Sciences of the University of Rwanda (Approval Notice: No 329/CMHS IRB/2021) and Ethics Committee of the University Teaching Hospital of Kigali (Review Approval Notice Ref.: EC/CHUK/002/2022). Written informed consent was obtained from all patients before recruitment and all procedures were conducted in accordance with the Declaration of Helsinki.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no conflicts of interest in this work. The funders had no role in the study design, collection, analyses, interpretation of data, writing of the manuscript, or decision to publish the results.