In our clinical work, patients and families often ask whether myelodysplastic syndrome (MDS) can be treated completely. Or can it be cured? To answer this question, we need to understand what kind of disease is myelodysplastic syndrome (MDS) first. Liu Xinjian, Department of Hematology, Henan Cancer Hospital
Myelodysplastic syndrome (MDS) is a heterogeneous group of hematopoietic stem cell disorders with three main features: (1) the bone marrow shows pathological hematopoiesis, including pathological hematopoiesis of the red blood cell system, white blood cell system and megakaryocytes. (2) Ineffective hematopoiesis of the bone marrow and the resulting hematocrit reduction. This includes simple erythrocytopenia, leukopenia, thrombocytopenia, and holocytopenia. It often manifests as simple erythrocytopenia and allohematocritopenia. (iii) There is a high risk of progression to acute myeloid leukemia, and according to foreign data approximately one-third of patients have to convert to acute myeloid leukemia.
Whether myelodysplastic syndrome (MDS) can be cured depends on three factors: ① disease factors ② patient factors ③ treatment factors. The following is a summary of these factors.
I. Disease factors
According to the WHO (World Health Organization) 2008 classification, myelodysplastic syndromes (MDS) are classified into the following groups.
① Refractory anemia with a lineage of pathological hematopoiesis (RCUD)
(ii) Refractory anemia with iron granulocytes (RARS)
(iii) Refractory anemia with multilineage pathological hematopoiesis (RCMD)
④refractory anemia with primitive cell excess (RAEB-1/RAEB-2)
⑤ Myelodysplastic syndrome unclassifiable (MDS-U)
⑥Myelodysplastic syndrome with independent 5q-
(vii) Refractory anemia with primitive cell excess in transformation (RAEB-T).
Different types of MDS are treated differently and the efficacy varies. In general, RCUD, RARS, and RCMD have relatively good therapeutic effects, while the rest have poor therapeutic effects.
In addition, the prognostic scoring system for myelodysplastic syndromes has different treatment outcomes for patients with different risk levels. low-threat intermediate-risk-1 in the IPSS scoring system has better treatment outcomes, while intermediate-risk-2 and high-risk have poor treatment outcomes. The revised IPSS scoring system (IPSS-R) is a better predictor of patient response to treatment than the IPSS.
II. Patient factors
Patient’s age, physical fitness score, co-morbidity status, organ reserve capacity, organ functional status, caregiver status, patient’s compliance, patient’s education level, patient’s psychological status, and patient’s economic status all influence patient’s treatment outcome.
Third, treatment factors
It is well known that the treatment effect of patients depends on the choice of treatment plan and the level of care. However, because myelodysplastic syndrome is a heterogeneous disease, diagnosis is very difficult, especially for low-risk MDS, and the diagnostic criteria are often mutually exclusive, making it possible for very few hospitals nationwide to actually diagnose MDS correctly, score the prognosis correctly, and select the correct treatment plan. There are also very few doctors who really specialize in MDS, so it is difficult for most MDS patients to be treated according to the correct protocol.
(i) Hospital factors
At present, most of the hospitals above the prefectural level and a small number of county hospitals in China have established hematology departments and are diagnosing and treating MDS, but as far as I know, except for the MDS treatment center in Tianjin Institute of Hematology, the MDS treatment center in the hematology department of Shanghai Sixth People’s Hospital, the MDS treatment center in Zhejiang University Hospital, the anemia treatment center in the hematology department of Jiangsu Provincial People’s Hospital and the anemia ward in the hematology department of Henan Provincial Cancer Hospital, most of the hospitals are not able to treat MDS. Apart from the anemia ward, most hospitals above the provincial level do not have specialized departments and wards for the diagnosis and treatment of MDS. As mentioned above, MDS is a heterogeneous disease that is very difficult to diagnose and treat, and some of the patients with MDS diagnosed in other hospitals that we have seen are suffering from hematopenia caused by other diseases and cannot be diagnosed with MDS. The NCCN MDS treatment guidelines in the United States and the ELN MDS guidelines emphasize that MDS should be diagnosed at an experienced MDS treatment center. However, in China, due to the influence of various factors, most of them diagnose MDS based on only one bone marrow aspiration result, or also send specimens to third-party testing companies for many subtractive tests, but due to incomplete understanding and knowledge of the disease, they often fail to correctly diagnose, staging and prognostically group MDS, resulting in failure to properly treat patients rationally. We often encounter patients with MDS regardless of the typing and prognostic group, treated with drugs such as Conlivon (or Danazol), cyclosporine A, thalidomide, folic acid, vitamin B12, erythropoietin, etc., and even more so with iron for hematopoietic treatment. In conclusion, the diagnosis and treatment of MDS in China are not standardized, and there is an urgent need for strict hierarchical treatment.
The ideal diagnosis and treatment model for MDS should be as follows: the patient is suspected of having MDS at the local or county level hospital, the MDS treatment center at the provincial hospital correctly diagnoses, typing and prognosis groups, and the patient is returned to the local hospital for treatment. If the provincial hospital is still unable to diagnose, the national MDS treatment center in Tianjin and Shanghai will make further diagnosis and then return to the provincial hospital or the local city for treatment.
At present, most of the MDS patients in China are not properly diagnosed and treated due to the misunderstanding of the medical reform policy of “no major disease leaving the county” and the influence of profit-seeking behavior of some primary hospitals. According to the MDS incidence rate of about 5/100,000 in Europe and 3.75/100,000 in the United States, the MDS underdiagnosis rate in China should be very high. (There is no epidemiological data on the incidence of MDS in China).
(ii) Physician factors
The selection of the right doctor is a crucial factor for MDS patients to be diagnosed and treated correctly. Different doctors at the same level or in the same hospital may make different diagnoses and develop different treatment plans due to different attention to MDS, different knowledge of the disease, different experience in treatment, different mastery of new developments in MDS, and different attention to the patient’s disease. For example, we have a patient who was diagnosed with “aplastic anemia” at the Tianjin Institute of Hematology and saw a veteran specialist. We considered it to be MDS-RCMD after consultation, and then Professor Xiao Zhijian from Tianjin Institute of Hematology diagnosed it again and confirmed our diagnosis. We also often see patients with MDS who are not diagnosed at other hospitals of the same level, but after further examination we clarify the diagnosis. The reason for misdiagnosis is often an irregular diagnosis. We now diagnose a patient with MDS by first doing bone marrow aspiration examination and bone marrow biopsy at more than three sites, and by doing flow cytology test, karyotype analysis and FISH test, gene mutation and other molecular biology tests. A more comprehensive diagnosis, typing and prognostic stratification is made for the patient. For example, the diagnosis of one of our recent 36-year-old male patients is as follows.
Diagnosis: myelodysplastic syndrome-refractory anemia with multilineage pathological hematopoiesis (MDS-RCMD)
With: PNH clone, elevated LDH, EPO <500mU/ML, HLA-DR15 positive molecular adverse factors: SRSF2 positive
Why is the diagnosis so complex? Because each item of the diagnosis has its clinical significance. Firstly, we clarify the patient’s diagnosis and staging as: MDS-RCMD. secondly, we give the patient a prognostic score as: low risk group. Because IPSS:intermediate-risk-1WPSS:intermediate-risk groupIPSS-R:intermediate-risk group are all in the low-risk group, however, the three prognostic scoring systems have different prediction degrees, and the IPSS-R system has the highest prediction degree. The latest NCCN guidelines clearly state that: the IPSS-R prognostic scoring system is preferred, and patients in the IPSS-R:intermediate-risk group can be treated as the low-risk group first, and ineffective can be treated as the high-risk group The IPSS-R: patients in the intermediate-risk group can be treated as low-risk first, and those who fail can be treated as high-risk. The intermediate-risk group of the other two prognostic scoring systems cannot be treated in this way. Third, the presence of PNH clone and HLA-DR15 positivity predicted that it might be effective for immunosuppressive therapy; EPO <500mU/ML predicted that it might be effective for EPO therapy; LDH elevation and SRSF2 positivity suggested poor prognosis.
(iii) Factors of treatment regimen selection
The choice of treatment plan is the most critical factor to achieve the best treatment effect. The choice of treatment plan depends on the conditions of the hospital, on the correct and complete diagnosis and prognosis grouping, on the doctor’s mastery of new developments in MDS and treatment experience, etc. For example, in high-risk MDS patients treated with demethylation or lenalidomide, the bone marrow is heavily suppressed, and if the ward conditions are not good or the care conditions are not good, it is easy to cause serious life-threatening infections. Sometimes, inaccurate diagnostic staging leads to inaccurate treatment plan selection. The NCCN guidelines on clinical practice for MDS are updated at least twice a year, and the European Leukemia Network (ELN) recommendations for the diagnosis and treatment of MDS are updated once a year, which requires our professional MDS doctors to keep abreast of these new developments in order to make the most appropriate treatment plans for our patients. However, these guidelines and recommendations are all in English, and few physicians are willing to make the effort to read these documents carefully. Coupled with the fact that hematologists currently prefer to work on leukemia, lymphoma, and myeloma, which are well diagnosed and well treated, few hematologists are willing to focus on these anemic diseases such as MDS, which are difficult to diagnose and difficult to treat. At present, in China, most of the well-known hematologists are specialized in leukemia, lymphoma, myeloma and hemostasis thrombosis, so there are relatively few doctors in our country who focus on and are proficient in MDS diagnosis and treatment. If you search online, you may find many MDS specialists, in fact, there are not many real MDS specialists.