Overview of myelosclerosis
Myelosclerosis, i.e., myelosclerosis, primary myelofibrosis, belongs to a type of chronic myeloproliferative neoplasms, whose lesions include varying degrees of myelofibroblastic tissue proliferation and myeloid metaplasia of extramedullary hematopoietic tissues. It is most common in patients over 35 years of age. Some patients showed naïve red blood cells and white blood cells, manifesting leukemia blood picture. Most patients have hepatosplenomegaly.
Etiology
The underlying etiology is unknown. However, modern medical research has confirmed that activation of the JAK/STAT pathway caused by mutations in driver genes such as JAK2V617F, CALR, MPL, etc. is an important pathogenesis of this type of disease, and that targeting of this pathway abnormality can be treated with targeted drugs. The main pathological changes in this disease are the degeneration of bone marrow tissue into fibrous tissue and the reduction of hematopoietic tissue.
Symptoms
It is a hematologic disease characterized by anemia, with onset between 35 and 70 years of age, mostly over 50 years of age, in both sexes. There is bone pain, anemia, bleeding tendency, splenomegaly, and secondary gout.
Examination
1. Blood picture
Reticulocytosis, young granulocytes and young erythrocytes in the peripheral blood, increased white blood cell count, usually in (10-30) × 109/L.
2. Imaging
(1) X-ray and CT: the vertebral body of the spine, the bones of the limbs, the proximal femur and acetabulum, the proximal humerus and the scapular glenoid are obvious. There are signs of osteosclerosis, uneven increase in bone density, accompanied by speckled translucent areas, forming the so-called “hairy glass”-like changes.
(2) MRI: It shows thickening of the bone cortex and changes in the bone shape, and at the same time, obvious bone marrow signal abnormality can be seen, and the bone marrow signal changes in MRI can be seen earlier than those in plain films.
3. Bone marrow examination
Bone marrow smear has low proliferation of nucleated cells, and bone marrow biopsy shows a large amount of reticulated fibrous tissue, which is the basis for the diagnosis of this disease.
4. Genetic examination
The examination of driver genes such as JAK2V617F, CALR, MPL, and non-driver genes such as ASXL1 and TET2 is important, which can clarify the diagnosis and predict the prognosis.
Diagnosis
Diagnosis can be made by meeting three major criteria and two minor criteria.
1. Major criteria
(1) Proliferation and aggregation of megakaryocytes with heterogeneity (megakaryocytes of different sizes, inconsistent nucleoplasmic ratios, dense chromatin, globular or irregular folding), often accompanied by reticulation or (and) collagen fiber hyperplasia.
(2) Except for true erythrocytosis (PV), chronic granulocytic leukemia, hemolytic anemia, or other myeloid neoplasms.
(3) Presence of JAK2V617 mutation or other clonal markers (e.g., MPLW515K/L), or in the absence of clonal markers, infection, autoimmune or other chronic inflammatory disease, hairy cell leukemia or other lymphoid neoplasms, metastatic neoplasms, or chronic toxic myelopathy.
2. Secondary criteria
(1) Young granulocytic erythrocytosis.
(2) Increased serum lactate dehydrogenase (LDH) levels.
(3) Anemia.
(4) Splenomegaly.
Treatment
Symptomatic treatment is the mainstay. Bleeding or severe anemia should be fed fresh whole blood.
1. Correction of anemia
Androgens and protein synthesizers have the effect of improving bone marrow hematopoiesis. Commonly used drugs are testosterone propionate (intramuscular injection) or oral stanozolol, testosterone undecanoate and other drugs. Thalidomide and corticosteroids also have some effect.
2. Cytostatic drug therapy
It can inhibit the abnormal proliferation of bone marrow hematopoietic tissues, and at the same time can inhibit the immune pathogenesis. Commonly used drugs are hydroxyurea, 6-mercaptopurine (leukovorin), interferon and other drugs.
3. Targeted therapy
Current research has confirmed that rucotinib, a JAK/STAT pathway inhibitor, can prolong patients’ lives, improve symptoms, shrink the spleen and even reverse myelofibrosis. Rucotinib can be used in all primary myelofibrosis patients, not just those with the JAK2V617F mutation.
4. Allogeneic hematopoietic stem cell transplantation
Allogeneic hematopoietic stem cell transplantation can cure this chronic neoplastic disease, but because of the cost and risk of treatment, it is difficult to promote its use in all patients.
5. Splenectomy
(1) Splenectomy is limited to the giant spleen with obvious compression symptoms or persistent pain caused by splenic necrosis.
(2) Patients with intractable hemolysis or thrombocytopenia caused by hypersplenism, which is ineffective in drug treatment and requires repeated blood transfusion for a long period of time, but the hematopoietic function has not been completely lost.
(3) Accompanied by portal hypertension complicating rupture and bleeding of esophageal varices.