2019 Volume 42 Issue 10 Pages 1651-1657
Patients with myelodysplastic syndrome (MDS) often require blood transfusion and anticancer therapy; however, elderly patients are intolerant to the associated side effects of anticancer therapy. Because L-leucine can be used to treat Diamond–Blackfan anemia, which is caused by defects in ribosomal protein (RP) genes, resulting in increased in vivo hemoglobin synthesis, it is possible that some MDS patients who have aberrations in their RP genes could also be effectively treated with L-leucine. In the present study, we investigated the effects of L-leucine on hematopoietic function (reticulocyte count), red blood cell count, and hemoglobin level in MDS patients. We administered L-leucine (1.8 g, twice daily, 3 d/week) with oral vitamin B6 supplements to a final cohort of eight MDS patients for 15 (interquartile range: 11–18) weeks. We assessed the patients at 10 ± 2 weeks after therapy initiation. Only the absolute reticulocyte count was affected, improving in 6/8 (75%) patients. The median absolute reticulocyte count was 3.5 × 104 (range: 2.7–6.4 × 104) cells/µL, an increase of 0.5 × 104 (range: 0.2–0.7 × 104) cells/µL. At 10 weeks, there was only one case of an improved hemoglobin level. Non-hematological adverse events of grade 3 were observed one raised triglycerides. These data suggest that L-leucine has little effect on MDS. However, it may contribute to the recovery of hematopoietic function, futher study be desired.
Myelodysplastic syndrome (MDS) comprises a group of diseases in which blood stem cells proliferate in a clonal manner. MDS is characterized by bone marrow hyperplasia, a decrease in red blood cells, white blood cells, and platelets (ineffective hematopoiesis), and dysplastic changes in blood cells. Patients often suffer from anemia and are at an increased risk of developing acute myeloid leukemia as the condition progresses. In many cases, the patients are elderly, and approximately half exhibit some form of a chromosomal abnormality; 20–30% have a deletion of chromosome 5q, and 14% have other complex chromosomal aberrations.1)
Based on the severity, MDS can be categorized as low-risk MDS, in which the primary symptom is hematopoietic failure, or high-risk MDS, in which the primary symptoms include tumor growth and leukemia. For low-risk cases, treatment includes conservative therapy, immunosuppressive therapy, anticancer therapy (e.g., lenalidomide and azacitidine),2–5) and allogeneic hematopoietic stem cell transplantation. Azacitidine administration has been reported as effective,4,5) however often some elderly cases are difficult to continue due to that adverse events.
MDS pathogenesis is attributed to abnormalities in the RNA splicing mechanism and aberrations in ribosomal protein (RP) genes; however, the specific details of this process remain unelucidated.6) In a 7-year-old female patient with Diamond–Blackfan anemia (DBA), the oral administration of 500 mg L-leucine twice daily improved symptoms 6 months after treatment initiation and for 9 months thereafter.7) Subsequent studies revealed that DBA is caused by defects in RP genes and demonstrated that L-leucine enhances the ability to synthesize hemoglobin in modeled DBA and del(5q) MDS in zebrafish.8,9) Patients with chromosome 5q deletion syndrome (5q-syndrome), a type of MDS, lack the RPS14 gene. This gene has been identified as involved in ribosomal functions, indicating a striking similarity to the pathogenesis of DBA.10) A minority of MDS patients may develop RP abnormalities. Because L-leucine attenuates the expression of p53 transcriptional targets, which play a pivotal role in inducing abnormal RPs in hematopoietic progenitor cells, it may suppress the biosynthesis of aberrant RPs.8) Therefore, we aimed to conduct a pilot study to verify whether L-leucine is effective in certain MDS patients.
Patients diagnosed with MDS classified as refractory anemia (RA), refractory anemia with ring sideroblasts, refractory cytopenia with multilineage dysplasia (RCMD), refractory anemia with excess blasts type 1 (RAEB-1), unclassified MDS, or 5q-syndrome according to the WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, 4th edition11) were enrolled in the present study. The patients were aged 40–90 years, and informed consent was obtained from each patient prior to study participation.
All patients had an Eastern Cooperative Oncology Group performance status (PS) of 0–2 and adequate hepatic (serum bilirubin <2.0 mg/dL), cardiac (no serious abnormalities on electrocardiogram), renal (serum creatinine <2.0 mg/dL), and lung functions at the time of screening. Patients were enrolled in the study if they met any of the following criteria: (a) hemoglobin ≤11 g/dL or receiving red cell concentrate blood transfusions once every 1–8 weeks; (b) platelet count ≤10.0 × 104/µL; or (c) neutrophil count ≤1000 cells/µL.
Exclusion CriteriaMDS patients with refractory anemia with excess blasts type 2 (RAEB-2) were excluded. Patients with pancytopenia due to other conditions, a blast cell ratio of >10% with substantial increases in blast cell numbers over time, a requirement for anticancer therapy, and a life expectancy ≤3 months were also excluded. Patients suffering from renal failure, an uncontrolled infectious disease (including active tuberculosis), hepatic cirrhosis, severe mental illness, pregnancy, severe heart disease, or severe lung disease were not enrolled.
InvestigationsStudy DesignThis was a single-arm study that used an enrollment system. Both inpatients and outpatients were eligible for enrollment February 2013 to March 2015 at Fujita Health University Hospital. With regard to the criteria for discontinuation, patients were permitted to withdraw from the study at will, at their family’s request, or if further continuation was deemed impractical by the study investigator (e.g., an aggravation of underlying symptoms). Patients were also excluded if they ceased to present at the hospital (e.g., transfer or death).
The patients were administered oral L-leucine (1.8 g, twice daily, 3 d/week) with oral vitamin B6 supplements (30 mg, twice daily, 3 d/week). Vitamin B6 supplementation was required as a coenzyme for proteases and aminotransferases.12) After 3 weeks of treatment, the attending physician determined whether the patients could continue receiving the medications on the basis of blood test results. If a patient complained of gastrointestinal symptoms (e.g., stomach discomfort), the dosing regimen was changed to a twice-weekly oral administration of both the medications.
No restrictions were placed on other concomitant medications or treatments. Transfusion of red blood cells and platelets as well as antibiotic administration in case of fever was left to the discretion of the attending physician. The use of hydrocortisone as an antipyretic was also permitted. Treatment was continued if the attending physician concluded that the administration of L-leucine was effective or if the patient wished to continue the treatment. When a patient was prematurely withdrawn from the clinical study (e.g., because of adverse events), the previous treatment was resumed.
MedicationL-Leucine therapy was administered using 300 mg L-leucine capsules (Adaptogen Pharmaceutical Co., Ltd., Tajimi, Japan). The L-leucine capsules were stored in the hospital pharmacy under light-shielded non-humid conditions at 20–25°C to ensure the requisite quality. To improve patient compliance with the dosing regimen, the L-leucine capsules were separated into packages containing six capsules each (a single dose), and medication ingestion was recorded to ensure adherence to the dosing regimen. At the start of the study, the pharmacist-in-charge instructed the patients on how the L-leucine capsules and vitamin B6 supplements should be ingested, at what dose they should be ingested, and how the record sheet should be completed.12) The pharmacist then confirmed the patient’s ingestion status from the record sheet upon issuing a prescription or at the time of an outpatient visit. At the end of the clinical study, the pharmacist collected the record sheet and any remaining medication from each patient.
AssessmentThe reticulocyte count ratio (%), absolute reticulocyte count (×104 cells/µL), hemoglobin level (g/dL), red blood cell count (×104 cells/µL), hematocrit level (%), and platelet count (×104/µL) were measured six times: once at baseline; at least twice at weeks 2, 4, 6, or 8; once at week 10 (if unavailable, this measurement was substituted with any value obtained within ±2 weeks); and at least twice at weeks 12, 16, 20, or 24. Efficacy was evaluated at week 10, and the administration of L-leucine and vitamin B6 was immediately discontinued if the medication was deemed ineffective. However, if a request was made by the patient, the dosing period was extended by 2 weeks before being discontinued.
The efficacy criteria were set as follows: (1) erythroblasts: increase in hemoglobin level ≥1.5 g/dL from the baseline or decrease in the use of red cell concentrate in mannitol adenine phosphate solution by ≥4 units within 2 months; (2) platelets: increase in platelet count to ≥30000/µL in patients with a previous count of ≥20000/µL or 100% improvement with respect to the baseline in patients with a previous count of <20000/µL; (3) neutrophils: 100% improvement with respect to the baseline and above 500/mm3; (4) other parameters: ≥50% decrease in blast cell ratio with respect to the baseline in bone marrow aspiration and peripheral blood examination.
The efficacy level was classified as “effective” when any of the above criteria were satisfied, “moderately effective” when none of the above criteria was satisfied but a trend toward improvement was evident for all the criteria or when a patient noted clear improvements in their general condition, “unchanged” when the values neither changed nor deteriorated with respect to the baseline, and “aggravated” when the values decreased with respect to the baseline. Evaluation as either “effective” or “moderately effective” was regarded as an effective result. If only a patient noted “clear improvements,” the patient could be classified as “moderately effective.” Using the medication management table, we checked medication adherence and subjective symptoms (improving fatigue) at the time of outpatient prescribed medication. The complaints about improvement of the symptom at the time of outpatient examination were to listen from the patient or investigated from the medical record.
Adverse events were assessed using the National Cancer Institute-Common Terminology Criteria for Adverse Events 4.0.
Statistical AnalysisData are presented as medians with interquartile ranges. Statistical Package for the Social Sciences 22.0 (IBM Corporation, Armonk, NY, U.S.A.) was used for all statistical analyses.
EthicsThe present study was approved by the Institutional Review Board of the Fujita Health University School of Medicine and conformed to the provisions of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The study was performed according to the institutional guidelines. Informed written consent was obtained from all participants.
Of the ten patients enrolled in our present study, two met the exclusion criteria (one had MDS RAEB-2, and the other was diagnosed with pure red cell aplasia and aplastic anemia) and were disqualified. The final cohort consisted of eight patients showed Table 1. Eight patients consisted seven men and one woman with a median age of 77.0 (range: 69.3–79.5) years. According to the WHO classification, four patients were classified as RA, two as RCMD, and two as RAEB-1. Six of the patients had a PS of 0 and two had a PS of 1. Because all patients could be treated as outpatients, they received ambulatory care.
| Patient No. | Age (yr) | Sex | Diagnosis (WHO) | Peripheral blood | RBC before study (U/interval) | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Reticulocyte absolute counts (×10*4/µL) | Reticulocyte ratio (%) | Red blood cell counts (×10*4/µL) | Hemoglobin level (g/dL) | Hematocrit (%) | Platelet count (×10*4/µL) | |||||
| 1 | 79 | M | RCMD | 3.6 | 1.8 | 204 | 6.4 | 19.8 | 11.5 | 2/month |
| 2 | 79 | M | RCMD | 2.5 | 1.5 | 171 | 5.9 | 17.4 | 2.2 | 2/3–4 weeks |
| 3 | 72 | M | RA | 3.9 | 1.2 | 330 | 11.7 | 34.3 | 5.8 | — |
| 4 | 84 | M | RAEB-1 | 5.9 | 2.8 | 214 | 6.9 | 21.4 | 5.6 | 2/3 weeks |
| 5 | 48 | M | RA | 2.5 | 0.8 | 314 | 9.5 | 28.6 | 20.6 | — |
| 6 | 81 | F | RA | 4.4 | 1.9 | 236 | 8.6 | 25.7 | 1.0 | — |
| 7 | 61 | M | RAEB-1 | 3.4 | 1.7 | 202 | 7.3 | 20.9 | 7.2 | 2/3 weeks |
| 8 | 75 | M | RA | 9.5 | 3.9 | 246 | 9.1 | 28.7 | 21.0 | — |
RBC, packed red blood cell transfusions; RA, refractory anemia; RCMD, refractory cytopenia with multilineage dysplasia; RAEB, refractory anemia with excess blasts.
Table 2 presents the changes in the absolute reticulocyte count, which improved in 6/8 (75%) patients. The median absolute reticulocyte count at 10 weeks was 3.5 × 104 (range: 2.7–6.4 × 104) cells/µL, an increase of 0.5 × 104 (range: 0.2–0.7 × 104) cells/µL from the baseline.
| Patient No. | Baseline (×10*4 cells/µL) | 2–8 weeks (×10*4 cells/µL) | 10 weeks (×10*4 cells/µL) | 12–24 weeks (×10*4 cells/µL) |
|---|---|---|---|---|
| Value (% increase) | ||||
| 1 | 3.6 | 3.0–3.6 | 3.1 (−13.8) | 2.0–3.5 |
| 2 | 2.5 | 2.7–3.2 | 2.7 (8.0) | 1.7–3.6 |
| 3 | 3.9 | 4.0 | 4.0 (2.5) | 3.9–4.6 |
| 4 | 5.9 | 6.7 | 6.7 (13.5) | 3.3–5.1 |
| 5 | 2.5 | 2.8–3.4 | 2.8 (12.0) | 2.6–3.5 |
| 6 | 4.4 | 5.2–6.4 | 6.4 (45.4) | 5.5–6.3 |
| 7 | 3.4 | 1.4–2.6 | 0 (Salient decrease) | 0 |
| 8 | 9.5 | 10.6–10.8 | 10.2 (7.3) | 6.8–10.8 |
Data were obtained before L-leucine therapy initiation and at 2–24 weeks. Baseline and 10-week data is expressed as a value. Data at 2–8 and 12–24 weeks are expressed as a range. Increased % is calculated as the % difference between the baseline and 10-week results.
Table 3 shows the serum hemoglobin levels. Only one patient exhibited a negligible improvement hemoglobin levels at 10 weeks, changing from a baseline of 7.9 (range: 6.8–9.2) to 7.5 (range: 6.1–8.9) g/dL after 10 weeks of L-leucine therapy.
| Patient No. | Baseline (g/dL) | 2–8 weeks (g/dL) | 10 weeks (g/dL) | 12–24 weeks (g/dL) |
|---|---|---|---|---|
| Value (% increase) | ||||
| 1 | 6.4 | 5.7–6.2 | 6.1 (−4.6) | 5.1–6.1 |
| 2 | 5.9 | 5.9–6.7 | 5.9 (0) | 5.3–7.0 |
| 3 | 11.7 | 10.9–11.1 | 11.1 (−5.1) | 10.5–10.7 |
| 4 | 6.9 | 6.9–7.4 | 5.0 (−27.5) | 6.5–7.1 |
| 5 | 9.5 | 9.5–9.6 | 9.6 (1.0) | 8.7–10.0 |
| 6 | 8.6 | 8.2–9.0 | 8.4 (−2.3) | 8.6–9.2 |
| 7 | 7.3 | 6.0–7.1 | 6.6 (−9.5) | 4.9–5.4 |
| 8 | 9.1 | 9.0–9.4 | 8.6 (−5.4) | 7.7–8.6 |
Data were obtained before L-leucine therapy initiation and at 2–24 weeks. Baseline and 10-week data is expressed as a value. Data at 2–8 and 12–24 weeks are expressed as a range. Increased % is calculated as the % difference between the baseline and 10-week results.
The median red blood cell count at baseline was 225.0 × 104 (range: 203.5–263 × 104) cells/µL and change to 225.5 × 104 (range: 192.2–256.7 × 104) at 10 weeks. Only 2 patients increased at 10 weeks from baseline.
Hematocrit LevelThe median hematocrit level at baseline was 23.5 (range: 20.6–28.6)% and change to 22.4 (range: 18.2–27.7)% at 10 weeks. Only 2 patients increased at 10 weeks from baseline.
Platelet CountThe median platelet count at baseline was 6.5 × 104 (range: 4.7–13.7)/µL and change to 4.8 (range: 2.2–14.1)/µL. 3 patients increased at 10 weeks from baseline.
EfficacyFigure 1 shows changing in laboratory parameters from pre-therapy (baseline) to 10 weeks. Table 4 shows administration period and outcome of L-leucine therapy. The dosing period of L-leucine was 12.5 (range: 10.0–16.8) weeks. None of the patients obtained the level of efficacy was evaluated “effective,” “moderately effective” in four patients, “unchanged” in two patients, and “aggravated” in two patients.
Data were obtained before L-leucine therapy and 10 weeks (±2 weeks) points during therapy in 7 patients evaluable for response. (□) RA, refractory anemia; (●) RCMD, refractory cytopenia with multilineage dysplasia; (△) RAEB-1, refractory anemia with excess blasts-1. Exclude 1 patients because administrated only 4 weeks.
| Patient no. | Administration period of L-leucine (week) | Cause of study discontinuation | Clinical response at 10 weeks |
|---|---|---|---|
| 1 | 10 | — | Unchanged |
| 2 | 20 | — | Moderately effective |
| 3 | 14 | — | Unchanged |
| 4 | 10 | — | Aggravated |
| 5 | 16 | — | Moderately effective |
| 6 | 11 | — | Moderately effective |
| 7 | 4 | Disease progression: MDS overt leukemia | Aggravated |
| 8 | 19 | — | Moderately effective |
Table 5 shows toxic effects observed during L-leucine therapy. No hematological events occurred during therapy. Non-hematological events of grade 3 were observed one raised triglycerides. AST and ALT raised 69 and 150 respectively after four weeks at initiated L-leucine therapy. After eleven weeks decreased 53 and 118, then it improved at baseline only by follow-up observation.
| Patient No. | Rash | Cheilitis | Nausea/vomiting | Anorexia | Diarrhea | Myalgia | Fatigue | Headache | Increased ALT/AST | Increased bilirubin |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | — | — | — | — | — | — | — | — | G1/G1 | — |
| 2 | — | — | —/G1 | — | G1 | — | G1 | — | — | — |
| 3 | — | — | — | — | — | — | — | — | — | — |
| 4 | — | — | — | G1 | — | — | G1 | — | G1/— | — |
| 5 | — | — | — | — | — | — | — | — | G3/G1 | — |
| 6 | G1 | — | — | — | — | — | — | — | — | — |
| 7 | — | — | — | — | — | — | — | — | — | NA |
| 8 | — | — | — | — | — | — | — | — | —/G1 | G1 |
Adverse events were assessed using the National Cancer Institute—Common Terminology Criteria for Adverse Events 4.0. ALT, Alanine aminotransferase; AST, Aspartate aminotransferase; G, Grade; NA, Not applicable.
In our study, oral administration of L-leucine to low-risk MDS patients over 10 weeks resulted in an increased absolute reticulocyte count (an index of hematopoietic functionality) in 6/8 patients. This study is a pilot study that evaluated the improvement effect and safety of L-leucine on hematopoietic function in Japanese MDS patients for the first time. The increase in reticulocyte count at 10 weeks is meaningful. In MDS patients, most of whom are elderly, daily administration of anticancer drugs can be burdensome, and sometimes only blood transfusion is performed. Therefore, we think that important to use L-leucine as an option for elderly low risk MDS patients. And L-leucine is relatively inexpensive. The fact that L-leucine is inexpensive compared to other chemotherapeutic drugs and transfusion therapy can be considered as one of the good options from the medical economic point of view. Moreover, to assess the adverse effects of leucine overdose, Pencharz et al.13) administered leucine to five healthy subjects in a stepwise manner at doses ranging from 50 to 1250 mg/kg/d. They found that a dose of 550 mg/kg/d was the safe upper limit of leucine intake. They also reported that a leucine overdose induced the oxidation of leucine and increased the blood ammonia concentration without affecting the alanine aminotransferase level and could lower blood sugar levels within the reference range without altering the plasma insulin concentration. As described above, although an overdose of leucine is likely to cause adverse drug reactions, the risk of inducing adverse drug reactions is considered to be low at a normal dose. The dose of 3.6 g/d adopted in our study translates to 60 mg/kg/d for a patient weighing 60 kg, which is much lower than the safe upper limit of leucine intake described by Pencharz et al. Also in the safety evaluation in this study, adverse event with grade 3 or higher was one liver dysfunction, and the safety at the set dose in this study was shown.
Steensma et al. setting MDS with isolated del(5q) were took L-leucine a dose of 1500 mg orally 3 times daily for 2 to 3 months.14) This study resulted none improvement in their cytopenias or transfusion needs. In the study of Steensma et al., the details of changes in each laboratory parameters were not described, and only 5q-MDS patients were targeted. So, direct comparison with our study was difficult. Whether the target for L-leucine therapy is total low risk MDS or only 5q-syndrome needs further investigation. Pospisilova et al.7) orally administered 500 mg L-leucine to a 7-year-old female patient with DBA twice daily over 9 months and noted a subsequent increase in the reticulocyte ratio and hemoglobin level and a decrease in the ferritin level 6 months after treatment administration. These effects persisted for 9 months. In the present study, we administered L-leucine to MDS patients with a median age of 77.0 (interquartile range: 69.3–79.5) years and observed an increase in the absolute reticulocyte count in 75% of the patients 10 weeks after treatment initiation. However, this did not reach an improvement in hemoglobin levels. In our study, the L-leucine treatment was not classified as “effective” for any patient. The differences in the frequency and duration of L-leucine administration between the two studies and our study may have affected the outcomes. Pospisilova et al. administered L-leucine to a 7-year-old child at a dose of 500 mg twice daily for 9 months (36 weeks), and we administered L-leucine to adult MDS patients at 1.8 g twice daily 3 times a week over 10 weeks or more. The dose of 3.6 g/d employed in our study is equivalent to 10.8 g/week when administered 3 times a week. According to Young’s formula,15,16) this equates to 4.0 g/week for a 7-year-old child. In contrast, Pospisilova et al. administered a dose of 1.0 g/d (i.e., 7.0 g/week), which was considerably higher than our dose. We set our dose lower than that in the study by Pospisilova et al. Our study was pilot study. We made a medication dose adjusted because our patients were relatively elderly. Elderly patients generally have a lower organ reserve than adult patients. We emphasized safety. In order to confirm the subjective symptoms on the next day of medication, we settled the administration method was 3 d per week. And we considered the dietary intake of L-leucine. We considered it as a 10-week evaluation for taking into consideration the available period for taking it. And the treatment after the end of L-leucine therapy was not specified.
Currently, doctors diagnose MDS according to the International Prognostic Scoring System (IPSS)17) and its revised version.18) IPSS classifies most MDS patients with a chief complaint of cytopenia derived from bone marrow failure rather than tumor growth into the low-risk group. To treat these patients, protein anabolism hormones and vitamins K and D are often used.19,20) In a clinical study involving Japanese patients, vitamins K2 and D3 were reported to be effective in low-risk patients20); however, because these were small-scale domestic clinical studies, these vitamins are not acknowledged as a recommended therapy for MDS. Despite the availability of several therapeutic modalities, there is no high-level evidence to draw solid conclusions. Another report noted that the effectiveness of immunosuppressants was similar to that of agents used for aplastic anemia (e.g., cyclosporin [CPA] and antithymocyte globulin [ATG]) in certain MDS patients. According to that report, immunosuppressants are particularly effective in patients with unclassifiable MDS accompanied by a deletion in chromosome 13q.21) However, the criteria for the use of immunosuppressive therapy remain unclear in several respects. Although some data imply the presence of abnormal lymphocyte responses,22) the exact pathology remains undetermined. Moreover, the use of CPA and ATG requires caution in patients with decreased renal function or elderly patients who are at high risk of adverse drug reactions. In contrast, L-leucine therapy is relatively safe in the elderly. It is worthwhile to carefully consider the effectiveness of L-leucine therapy in the future study.
Our study had some limitations. The small sample size of eight patients limited statistical precision. Over the 2-year study period, one patient was unable to continue treatment after week 19. Had this patient continued the treatment, some improvement in the subjective clinical symptoms and test values could have been observed. However, because this patient was elderly and could have been transferred to another hospital as an outpatient at any time, further extension of the dosing period was impractical. Furthermore, we have not examined gene mutations in this study. The genes recognized as being associated with MDS include those encoding DNA methylation enzymes (e.g., ten-eleven translocation-2 [TET2], isocitrate dehydrogenase 1/2 [IDH1/2], and (cytosine-5)-methyltransferase 3 [DNMT3]); histone methylation enzymes and epigenome-related factors (e.g., enhancer of zeste homolog 2 [EZH2] and additional sex comb-like 1 [ASXL1]; and splicing-related factors (e.g., splicing factor 3B subunit 1 [SF3B1]). After commencing this clinical study, mutations in these factors and their clinical significance gradually came to light.23–27) Because our study was conducted before we became aware of these various gene mutations, the genetic mutations of the subjects were not analyzed. Therefore, it was impossible to clarify which gene mutations associated with MDS could be treated most effectively with L-leucine therapy. Future studies should evaluate the effectiveness and safety of L-leucine therapy in relation to such gene aberrations.
In our study found that administering L-leucine to elderly low-risk MDS patients in Japanese increases the absolute reticulocyte count. It may contribute to the recovery of hematopoietic function, further study be desired. By examining the type of MDS in the subject, the dose of L-leucine, the administration period and blood concentration, recovery of hematopoietic function may lead to improvement of anemia.
We thank the participating patients for their contribution to this study and the pharmacy, hematology, and nursing staff of Fujita Health University Hospital who assisted with the study.
The authors declare no conflict of interest.
