Hydroxyurea treatment for adult sickle cell anemia patients in Kinshasa

Abstract

Background: Despite a high incidence of sickle cell anemia, hydroxyurea (HU) treatment is rarely used in the DR Congo. This study aims to assess the efficacy of HU, the incidence of side effects that may limit its use in adults and to determine the dose needed for clinical improvement in patients.

Methods: In a prospective study, patients received an initial dose of 15 mg/kg/day which was increased by 5 mg/kg every 6 months, up to a maximum of 30 mg/kg/day. The response and side effects to HU were evaluated biologically and clinically every 3 months during a 2‐year period.

Results: Seventy adult patients with a moderate or severe clinical phenotype initiated treatment. Only minor side effects were reported. At the end of the 2‐year treatment phase, 45 (64.3%) had dropped out, of whom 33 were without a clear reason. Clinical and biological improvement was more marked during the first year. There was a reduction in severe vaso‐occlusive crises (p < 0.001), need for transfusion (p < 0.001), and hospitalization days (p = 0.038). Fetal hemoglobin (HbF) levels increased on average 2.9 times after 12 months (p < 0.001). The increase in mean corpuscular volume was greater in the first year (p < 0.001) than in the second year (p = 0.041). The decrease in leukocytes (p < 0.001) was significant during the first year. In 70% of patients, the 20 mg/kg/day dose was needed to reach the 20% HbF threshold.

Conclusion: HU is effective and well tolerated. The magnitude of the response varies from one patient to another. Improvement of clinical manifestations is achieved in most patients with a relatively low dose. Effective implementation of HU treatment will require improved adherence to treatment.

Novelties:

1. This work shows the efficacy of hydroxyurea (HU) treatment of sickle cell anemia in adult patients in a low‐resource country.

2. HU treatment can result in clinical improvement despite the absence of biological changes.

3. The specific clinical relevance of this work is the need to continue treatment with HU even if clinical improvement is not immediate, as it may occur late in some patients.

1. BACKGROUND

Sub‐Saharan Africa bears a heavy burden of sickle cell anemia (SCA), the Democratic Republic of the Congo (DRC) being the third most affected country worldwide, alongside Nigeria and India [1]. In these low‐resource areas, SCA‐related morbidity and mortality are high, especially when a well‐structured health system is lacking and thus fails to provide patients with integrated and consistent care. The financial burden of health care falls entirely on their families. In low‐resource countries, emphasis is currently on supportive therapy, treating acute manifestations, and preventing infections whenever antibiotics are accessible. Blood transfusions, one of the key components of supportive treatment, carry a risk of immunologic side effects and transmitting infections such as hepatitis and HIV [2].

Treatment of SCA with hydroxyurea (HU) holds great potential to ameliorate the course of the disease, as it reduces the incidence of crises and complications associated with organ degeneration. Its effectiveness is well documented in high‐income countries, both in adults and children, resulting in its widespread use in these countries [3, 4, 5]. HU is currently the standard treatment for SCA in Africa [6, 7, 8]. Through its ability to induce fetal hemoglobin (HbF) production, HU inhibits HbS polymerization and subsequent vaso‐occlusion. In addition to this mechanism, HU also acts by reducing leukocytosis, platelets, and vascular adhesion factors [5]. These properties translate into a reduction in the incidence of acute and chronic complications, leading to improved quality of life and reduced mortality in affected patients. Several studies conducted in high‐income countries have demonstrated both its effectiveness and its safety [5]. However, there are only a few studies evaluating its effectiveness, conducted in low‐income settings where morbidity and mortality from SCA are high [1, 3]. To our knowledge, there is no study in the DRC on the treatment of adult patients with HU.

The aim of this study is to evaluate the effectiveness of HU in ameliorating disease severity in adults with SCA in an urban region in central Africa and to determine the optimal therapeutic dose regimen of HU in this setting.

2. METHODS

This is a prospective study conducted at the “Centre de Médecine Mixte et d'Anémie SS” located in Kinshasa, the capital of the DRC. The study was designed with two phases. An observation phase lasts 1 year, followed by the treatment phase with HU for 2 years. During the observation phase, the clinical history of each patient was recorded (acute and chronic complications, number of painful crises, transfusions, days of hospitalization) in order to determine the disease severity using the severity score proposed by Mikobi et al [9]. The diagnosis of SCA was verified by hemoglobin electrophoresis and molecular testing, and biological and hematological parameters were obtained. The blood was collected on ethylene‐diamine‐tetra‐acetic acid in two tubes of four milliliters each. The first tube was sent to the Laboratory of Biochemistry and Hematology of the Faculty of Pharmaceutical Sciences of the University of Kinshasa for the performance of hematological and biochemical tests. The complete blood count (WBC, RBC, FL, etc.) was performed with a HumaCount 60 TS machine; whereas the counting of reticulocytes was carried out by microscopy after staining with brilliant cresyl blue. Bilirubinemia and LDH were measured using a Humalyzer 2000 spectrophotometer.

The second tube was sent to the human genetics laboratory of the Faculty of Medicine of the University of Kinshasa. The electrophoresis for the quantification of the different types of hemoglobin was carried out with a Minicap (Sebia) Phoresis Rel 8.6.3 automaton. DNA from the patients was extracted by salting out method and SCA mutation analysis was done by PCR followed by a restriction enzyme digestion [10]. These initial clinical and laboratory parameters served as a baseline for evaluating the effect of HU treatment. Moreover, this allowed us to select patients fulfilling the clinical inclusion criteria as well as those with an anticipated high adherence to follow‐up. None of these patients had ever received HU treatment. The treatment protocol in the DRC includes folic acid, and analgesics if needed.

In the second treatment phase, patients were treated by HU for a period of 2 years. Depending on the date when each patient started treatment, this lasted from August 30, 2017 to May 16, 2020, in order to complete a follow‐up of 24 months for each patient. The study group consisted of molecularly proven SCA patients with the following inclusion criteria: adult patients aged between 18 and 40 years, a HbF rate lower than 15%, and a moderate or severe phenotype according to the severity score of Mikobi et al [9].

The starting daily dose of HU was 15 mg/kg. The weekly dose was calculated according to the patient's weight. The number of 500 mg capsules corresponding to this dose was divided over 5–7 consecutive days of the week. This daily dosage was taken once a day. The dose was increased by 5 mg/kg/day every 6 months to reach a maximal dose of 30 mg/kg/day or a maximally tolerated dose. The HbF level reached was not taken into account to adjust the HU dosage.

During the treatment phase, patients were invited to a monthly appointment for a clinical examination and drug replenishment. The response to HU was evaluated every 3 months by recording morbidity using the severity score and biological markers (HbF, LDH, WBC, MCV, platelets, and reticulocyte count). Medical visits, paraclinical exams, and treatment with HU were offered free of charge to patients during their follow‐up.

Patients were classified as responding or non‐responding based on biological and clinical criteria. Biological responders were patients who reached a maximum HbF level of at least 20% [11, 12, 13, 14], or a maximum HbF level equal to or higher than triple its initial value. Clinical response was defined as a reduction in acute clinical manifestations by at least 50% [15, 16]. This clinical response was assessed using a modified clinical Mikobi score, considering only the acute phenomena, since these can be modified by treatment in the short term. The following were included: the number of days of hospitalizations, the number of severe vaso‐occlusion crises, and the number of blood transfusions.

2.1. Statistical analyses

Data were recorded in an Excel sheet and analyzed with IBM SPSS Statistics 23.0 software. Categorical data were presented in the form of frequency tables. Quantitative variables were presented by measures of central tendency and dispersion (mean and standard deviation). The student's t‐test was used to compare means. The ANOVA test was used to compare the means of different groups. Logistic regression was used to measure the effect of a factor on the dichotomous qualitative response variable. The Student's t‐test was used to compare the means of paired samples. The level of statistical significance was defined by a p‐value less than 0.05.

3. RESULTS

During the observation phase, we collected data on 166 SCA patients, from which 70 were selected to start HU treatment (Figure 1). Patients with a mild clinical phenotype (n = 48) and patients already treated with HU, with a HbF level above 15%, pregnant women, and breastfeeding women were excluded from the study. Two patients with hip disease and 1 patient with hemiplegia were also excluded, due to their inability to reach the hospital for follow‐up. Four patients were deceased, eight were lost to follow‐up and 22 patients were not included due to poor adherence to follow‐up consultations during the observation year.

FIGURE 1.

Summary of the patients' inclusion process.

The treatment group consisted of 41 females (58.6%) and 29 males (41.4%) with an average age of 24.5 ± 5.5 years in females and 24 ± 4.2 years in males.

The SCA phenotype was moderate in 61 patients, including 38 females and 23 males, while it was severe in 3 females and 6 males.

By the end of the 2‐year treatment phase, 45 (64.3%) had left the study. Twelve reported a specific reason, including aesthetic concerns (HU‐induced skin rash (n = 1) and hyperpigmentation of the skin (n = 1)), pregnancy (n = 1), lack of perceived treatment benefit (n = 1), difficulties in taking blood samples (n = 1), change to traditional herbal treatment (n = 2), moved out of Kinshasa (n = 2) and the occurrence of hip disease (n = 2). One patient died in the context of tramadol addiction. The remaining 33 were lost to follow‐up without any apparent reason or explanation. Of this latter subgroup, 15 patients are reportedly alive, but we do not have information on their health state. We have no information on the remaining 18 patients. Nearly half of the dropouts (22/45) occurred during the first 3 months of treatment. The trend curve for patient retention in the study is similar among male and female patients (Figure S1). Adherence with treatment did not vary with age (p = 0.293) nor with sex (p = 0.936).

Comparing patients lost to follow‐up without an apparent reason during the first 3 months (n = 15) and those who left the study after 3 months (n = 18), there was no statistically significant difference in age (p = 0.36) or sex (p = 0.27). The mean initial severity score was not significantly higher in patients who dropped out before the end of the third month (11.7 ± 3.6) than in those who dropped out after 3 months of follow‐up (10.3 ± 5.4) (p = 0.40).

3.1. Side effects of HU treatment

HU was generally well tolerated. Some patients presented, during the first month of treatment, mild adverse effects such as increased appetite (n = 7), stomach pain (n = 2), and asthenia (n = 2). A maculopapular rash (n = 1) was reported during the second month of treatment. No patient had major signs of myelosuppression.

3.2. Response to HU treatment

The clinical response was larger during the first year of treatment. The 39 patients who completed 12 months of treatment showed a significant reduction in the number of days of hospitalization (from15 ± 38 to 2.3 ± 4.1; p = 0.038), the frequency of severe vaso‐occlusive crises (from 4.8 ± 6 events to 0.7 ± 1.1; p = < 0.001) and the number of transfusions (from 2.1 ± 2.8 per year to 0.5 ± 1.2; p < 0.001). The further improvement observed during the second year of treatment was not statistically significant compared to the end of year one (Table 1).

TABLE 1.

Evolution of acute clinical events observed in patients who have completed 1 or 2 years of treatment with hydroxyurea (HU).

	Number
Period of treatment	Days of hosp	Severe VOC	Transfusions
Patients who completed 1 year of treatment
start (n = 39)	15 ± 38	4.8 ± 6	2.1 ± 2.8
Year1 (n = 39)	2.3 ± 4.1	0.7 ± 1.1	0.5 ± 1.2
p‐value (Start‐Y1)	0.038	<0.001	<0.001
Patients who completed 2 years of treatment
start (n = 25)	19.6 ± 47.3	4.3 ± 3.4	1.2 ± 3
Year 1 (n = 25)	2.1 ± 4.1	0.7 ± 1.3	0.4 ± 0.9
Year2 (n = 25)	1 ± 2.2	0.5 ± 1.3	0.2 ± 0.6
p‐value (Y1 and Y2)	0.139	0.495	0.346
p‐value (Start‐Y2)	0.06	<0.001	0.012

Abbreviations: Hosp, hospitalization; VOC, vaso‐occlusive crises; Y1, year one; Y2, year two.

p‐value: Student's t‐test for paired samples.

After 1 year of treatment, the modified clinical score taking into account the acute manifestations of SCA (number of vaso‐occlusive crises, number of transfusions, and total number of hospitalization days) showed that 74.4% of patients (29/39) had a reduction in this score of at least 50% (Table 2). The modified clinical severity score did not change in two patients, while it increased in one patient.

TABLE 2.

Changes in the modified clinical score after 1 year of hydroxyurea (HU) treatment.

Decrease in the modified clinical score	Patients (n = 39)	%	Cumulative %
100%–75%	21	53.8	53.8
74%–50%	8	20.5	74.4
25%–49%	5	12.8	87.2
1%–24%	2	5.1	92.3
No change	2	5.1	97.4
Increase	1	2.6	100

We evaluated the evolution of biological parameters during HU treatment. In 25 patients who completed 2 years of treatment, we observed a mean increase in the HbF rate of 2.9‐fold at 12 months and 3.1‐fold at 24 months compared to baseline levels (p < 0.001). The increase in HbF level between 12 and 24 months of treatment was not significant (p = 0.706) (Table 3). There was a significant increase in MCV. This increase was more important during the first year (p < 0.001 and 0.003, respectively) than the second year (p = 0.041 and 0.947, respectively). Platelets, LDH, and total bilirubin showed a non‐significant decrease after 2 years of treatment, with p‐values of 0.378, 0.535, and 0.309. The decrease in WBC (p < 0.001), reticulocytes (p < 0.001), and indirect bilirubin (p = 0.019) was significant during the first year of treatment.

TABLE 3.

Evolution of biological parameters in patients who have completed 1 or 2 years of hydroxyurea (HU) treatment.

		Mean ± standard deviation (normal values)
Period of treatment	HbF (1 ‐ 2 %)	WBC (4−10x103/mm3)	RETICULOCYTES (20–80x103 /mm3)	LDH (230–460 UI/L)	MCV (75–96 fl)	MCHC (30–35 g/dl)	Platelets (150–450 x 103/mm3)	Tot bilirubin (0—1.1 mg/dl)	Ind bilirubin (0‐0.1 mg/dl)
Start (n = 39)	5.6 ± 3.5	12.2 ± 4.9	164.6 ± 111.9	1612 ± 731	83.1 ± 9.1	33.5 ± 1.7	434.2 ± 181.7	2.9 ± 2.3	2.3 ± 1.6
Y1 (n = 39)	15.7 ± 8.9	8.1 ± 2.6	47.8 ± 21.9	1533 ± 661	97 ± 15	32.3 ± 1.8	413.9 ± 213.3	2.4 ± 1.9	1.5 ± 1.7
Y2 (n = 25)	20.1 ± 12	8.2 ± 6.9	29.2 ± 13.8	1779.3 ± 999.5	128 ± 57	32 ± 1.1	377.4 ± 128.7	2.2 ± 1.5	1.7 ± 1.2
p‐value start—Y1 (n = 39)	<0.001	<0.001	<0.001	0.606	<0.001	0.003	0.746	0.27	0.019
p‐value Y1 – Y2 (n = 25)	0.706	0.545	0.007	0.392	0.041	0.947	0.856	0.738	0.377
p‐value start—Y2 (n = 25)	<0.001	0.036	<0.001	0.535	0.001	0.054	0.378	0.309	0.266

Abbreviations: HbF, fetal hemoglobin; ind bilirubin, indirect bilirubin; LDH, lactate dehydrogenase; MCV, mean corpuscular volume; MCHC, mean corpuscular hemoglobin content; Tot bilirubin, total bilirubin; WBC, white blood cells; Y1, year one; Y2, year 2.

p‐value: Student's t‐test for paired samples.

The dose of HU required to achieve the 20% HbF threshold and/or a HbF increase of at least three times its initial value varied from one patient to another. Data from 27 patients treated with HU who met these criteria showed that 19 (70%) patients required relatively low doses of HU (15‐20 mg/kg/day), while the remaining eight (30%) patients only reached these thresholds with higher doses (25–30 mg/kg/day) (Figure S2). The median dose necessary to reach the minimum threshold of 20% HbF was 20 mg/kg/day; whereas the dose necessary to reach three times the initial value of HbF was 15 mg/kg/day (range 15–30 mg/kg/day).

After 1 year of HU treatment, 29 of 39 patients (74%) showed a good clinical response, that is, a reduction in severity score by at least 50% (Table 4). The mean reduction in the modified clinical score was 68.8%. In 15 of 39 patients, this was associated with a concomitant biological response based on HbF levels. However, in these 14 patients who showed a good clinical response without a significant increase in HbF, there was a decrease in WBC (15%) and in the absolute number of neutrophils (42%). Of the 10 patients who did not show a clinical response during year one and completed a second year of HU treatment, an additional five had a good clinical response. Thus, in total; 34/39 (87.2%) patients responded clinically well to HU treatment.

TABLE 4.

Response to hydroxyurea (HU) treatment after 1 year.

			Biological response
	Response		Yes	No
Clinical response	Yes	29 (74%)	15	14
	No	10 (26%)	5	5
			20 (51%)	19 (49%)

A good biological response was observed in 20 out of 39 patients during the first year of treatment. Of the 19 non‐responders, 10 continued treatment during year 2, and six showed a good biological response at the end of year 2. The biological response observed during the second year of treatment was good in 21/25 patients. Of the four patients who did not have a good biological response, three had a good clinical response, while the remaining patient showed a deterioration in his clinical response at year 2 after an improvement in this response at the end of year 1 (Table 5).

TABLE 5.

Response to hydroxyurea (HU) treatment after 2 years.

			Biological response
	Response		Yes	No
Clinical response	Yes	21 (84%)	18	3
	No	4 (16%)	3	1
			21 (84%)	4 (16%)

The biological response was not always associated with the clinical response as we observed discordance in some patients. At the end of the second year of HU, we observed both positive clinical and biological responses in 18/25 patients (72%). Biological improvement without clinical improvement was observed in three patients; while three patients had clinical improvement without biological improvement. One patient did not respond clinically or biologically. None of the baseline biological parameters tested could predict a good clinical response (Tables S1 and S2).

4. DISCUSSION

This prospective study, aimed at assessing the efficacy of HU treatment in adult SCA patients living in Kinshasa/DRC, clearly shows clinical and biological improvement in the majority of patients. The most important short‐term benefit of HU treatment was a reduced number of sickle cell crises and the associated need for hospitalizations and transfusions. The impact of this treatment was more significant during the first year. Further improvement was observed during the second year of treatment, even though this did not reach statistical significance, likely due to the low number of patients. This emphasizes the importance of continuing treatment in patients who do not show a clear improvement during the first year of treatment.

In parallel with the clinical effects, we also observed in this cohort clear changes in biological parameters in response to HU treatment, namely an increase in HbF levels and MCV, with a reduction in WBCs and reticulocytes [17]. The significant decrease in indirect bilirubin is explained by a reduction in hemolysis. However, in our cohort, we did not observe a concomitant decrease in LDH. This enzyme is a non‐specific marker of hemolysis because it is found in several tissues of the human body (heart, skeletal muscles, liver, erythrocytes, etc.). Reduced LDH levels secondary to reduced hemolysis in response to HU could have been counterbalanced by an increased LDH release secondary to other disorders such as hemolytic anemia due to malaria, obstructive hepatitis, or stroke [18].

The bilirubin level can be influenced by hepatobiliary complications (hepatitis, cholelithiasis) of sickle cell disease which are linked to chronic hemolysis and repeated blood transfusions. Their frequency increases with the age of the patient [19, 20]. The induction of HbF production is the most important biological effect of HU treatment, in SCA since HbF has a protective role against acute and chronic complications of SCA. This is exemplified by the mild clinical phenotype in SCA patients observed in association with elevated baseline HbF levels [15].

HbF is therefore considered as a surrogate parameter to evaluate response to HU treatment. After 1 year of treatment, half of the clinical responders did not show a biological response. It is recognized that the clinical effects of HU appear within a few weeks after initiation of treatment, while the biological effects often appear within a period of 6–8 months and are dose‐dependent [16]. This suggests that a clinical response in the absence of a substantial increase in HbF may be related to other mechanisms of action of HU.

For instance, HU‐induced myelosuppression causes a reduction in the production of neutrophils, reticulocytes, and platelets. In this cohort, patients who presented a good clinical response without a sufficient increase in HbF had a reduction in WBCs and in the absolute number of neutrophils. Also, HU reduces the expression of adhesive molecules by neutrophils and reticulocytes that interact with vascular endothelia. This leads to endothelial damage resulting in vaso‐occlusive events and organ damage. The clinical improvement is also related to morphological and physiological changes occurring in circulating erythrocytes, resulting in better hydration and better deformability, thereby reducing the risk of sickling and hemolysis [15, 17].

Of the responders reaching the target HbF level, seventy percent did so with a relatively low dose of HU, between 15 and 20 mg/kg/day. This variability in response to HU is related to pharmacokinetic and pharmacodynamic differences inherent in each individual [21]. A recent review of genetic factors associated with HbF response to HU treatment identified 50 different SNPs in 17 genes [22]. This knowledge may lead to the development of a polygenic score to stratify patients according to their expected HU response, which could allow to define the required therapeutic dose at the start without the risk of reaching toxic limits and minimize the cost of treatment.

There is variability in the pharmacokinetics of HU between individuals [21] such that some patients require a higher dose of HU to reach the expected clinical and biological improvement. This variability could be responsible for the continued change in certain parameters (reticulocytes, MCV) after the first year of treatment. Moreover, in this cohort, the dose of HU gradually increased also during the second year. Also, we cannot exclude variability in adherence to HU treatment or individual differences in response to HU treatment which could explain the observed changes in MCV [8].

Hydroxyurea tolerance was good as only a minority of patients showed side effects, which were minor. This is in line with other African studies both in children and adults [7, 16] and in adult patients from America [12]. This local experience provides an argument to reassure patients for whom fear of side effects constitutes a barrier to accepting HU treatment.

Despite the high clinical effectiveness of HU treatment in this cohort, with limited side effects, we observed a very high dropout of almost two‐thirds after 2 years. Of these, half occurred within the first 3 months. We did not formally study the reasons, but possible factors stated in the literature include the fear of HU side effects, the lack of perceived immediate benefit of the treatment, and the non‐encouraging prospect of taking treatment in the long course [12, 23]. Since the perceived lack of benefit is a major reason for discontinuation of the treatment, the clinical improvement we observed is an important argument to encourage patients to continue with the treatment [7, 16]. In addition, in a setting where there is no structured social security system, the inability of poor patients to cope with the financial constraint linked to regular visits to the hospital for follow‐up may be another factor explaining drop‐out [24]. In the present trial, we only provided patients with free HU treatment and paid the costs of biological testing, but we were not able to take care of other health problems that arose during this follow‐up period. It is a good hypothesis that starting HU at a younger age might improve adherence, but in a trial performed by our group in children (manuscript in preparation), we also observed a high rate of dropout of 45% after 2 years (compared to 65% in the present study in adults). At the individual level, we would propose to identify, for each SCA patient a trusted person, who could support the patient in taking the medication and adhere to the regular follow‐up schemes. Patient advocacy groups exist, but they do not play a major role in supporting adherence to follow‐up and treatment. However, educating patients through their associations may be valuable.

We believe the main hurdle is poorly accessible and affordable health facilities in the country, where most patients cannot afford to pay for the expenses linked to follow‐up and treatment of complications.

At inclusion, the issue of pregnancy was discussed with all female patients, pointing out that when pregnant, they need to stop the medication. They were reassured also that this medication would not affect their fertility. We cannot exclude the possibility that some young women left the study because they wanted to become pregnant, and avoid any harm to their baby by taking HU, since for most patients who dropped out, we had no follow‐up. Some men could also have left the study because of the fear of infertility linked to taking HU [25]. Several studies have shown that the spermogram is altered in patients who receive HU [26, 27]. However, this alteration returns to normal in most male patients after discontinuation of HU therapy [28].

5. CONCLUSION

HU is an effective treatment for SCA patients, with good clinical and biological efficacy. There is individual variability in the magnitude of response to treatment. Substantial clinical and biological improvements were obtained soon after the start of treatment, with a dose of between 15 and 20 mg/kg/day. This treatment must be continued to maintain the clinical or biological improvement obtained. As this study was characterized by a high dropout rate, it would be useful to consider a larger cohort in order to have a more consistent evaluation of the anticipation of the response to HU treatment.

Close contact must be maintained between caregivers and patients in order to reassure them about treatment‐related concerns and make them aware of the need for well‐monitored HU treatment [29].

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

FUNDING INFORMATION

This study was funded by VLIR‐UOS, and supported by the Chair ‘Genetics in the DRCongo’ (KU Leuven, holder K. Devriendt).

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non‐financial interest in the subject matter or materials discussed in this manuscript.

Kabuyi PL. Hydroxyurea treatment for adult sickle cell anemia patients in Kinshasa, Dryad, Dataset. 2023. https://doi.org/10.5061/dryad.nzs7h44w8

ETHICS STATEMENT

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the School of Public Health of the University of Kinshasa (November 30, 2016, ESP/CE/079/2016), DRC.

Supporting information

Supporting Information

Kabuyi PL, Mbayabo G, Ngole M, Zola AL, Race V, Matthijs G, et al. Hydroxyurea treatment for adult sickle cell anemia patients in Kinshasa. eJHaem. 2023;4:595–601. 10.1002/jha2.735

DATA AVAILABILITY STATEMENT

The data supporting the conclusions of this study are freely available at: