Idiopathic myelofibrosis - diagnosis and treatment

Neoplastic myeloproliferative disease, characterized by anemia, rejuvenation of granulocyte cells, bone marrow fibrosis, splenomegaly and the appearance of extramedullary foci of hematopoiesis. The etiology is unknown.

CLINICAL PICTURE AND TYPICAL CURRENT



  • 1. General symptoms: general weakness (in 50-70% of patients), lack of appetite (in <20%), потеря массы тела, субфебрилитет, одышка, тахикардия, ночная потливость, зуд, костно-суставная боль (преимущественно нижних конечностей), истощения.

  • 2. Symptoms associated with myelofibrosis and extramedullary hematopoiesis: splenomegaly (at the time of diagnosis in> 90% of patients, 2/3 - significant), can cause swelling of the lower extremities due to compression of the veins, swelling, pain in case of spleen infarction, increase in liver size (40-70%), secondary hypertension, thrombocytopenic purpura, symptoms of anemia, manifestations associated with extramedullary foci of hematopoiesis - more often in the thoracic area spinal cord compression, lymph nodes, pleura (pleural fluid), pulmonary (pulmonary hypertension), pericardium, peritoneum (ascites), skin (nodules), bladder (dysuria)

  • Typical course: first - asymptomatic, manifestations of increasing anemia, thrombocytopenia and myeloid metaplasia in the spleen and liver.In the terminal stage, hepatic insufficiency predominates. The average life expectancy is 5 years. Transformation in AML develops in 20% of patients.


  • DIAGNOSIS



    Auxiliary studies

    1. General analysis of peripheral blood: normocytic anemia; decreased the number of white blood cells, or slightly increased, may be normal; the number of platelets may be increased (in the prefibromatic phase), normal or decreased (in the late stages of the disease), morphological disorders and platelet function; in the swab of aniso- and poikilocytosis of erythrocytes; show a drop-shaped erythrocyte, as well as erythroblasts and youth granulocyte forms (leukotriitroblastoz).

    2. Study of the bone marrow is the only cytological examination usually does not allow you to establish a diagnosis. At the initial stages, the bone marrow of hyperclitinium with the presence of atypical megakaryocytes, later, in the phase of myelofibrosis and sclerosis, the sample can not be aspirated; requires trepanobiopsy - reveals an increased number of reticular and collagen fibers, a few residual foci of hematopoiesis.

    3. Molecular studies: a mutation of the V617F gene of JAK-2 (in ≤50%) or a mutation of the MPL gene. Negative result of BCR-ABL.

    Diagnostic criteria



    It is necessary to have all the large criteria and 2 small ones.

    1. Big criteria:

  • 1) a typical picture of trepanobioptate;

  • 2) exclusion of true polycythemia, CML, MDS and other tumor diseases of the myeloid series;

  • 3) the presence of mutation V617F gene JAK-2 or other clonal marker, and if they are not found - the absence of signs of secondary myelofibrosis, as manifestations of other oncological or inflammatory diseases (reactive myelofibrosis).


  • 2. Small criteria:

  • 1) leukotriitroblastoz in the peripheral blood;

  • 2) increase of LDH in serum;

  • 3) anemia;

  • 4) splenomegaly.


  • Differential diagnosis



  • 1. Myelofibrosis in other tumor diseases: true polycythemia, special thrombocythemia, CML, acute megakaryoblastic leukemia, acute panmyelosis with myelofibrosis, MDS, CMML, hairy-cystic leukemia, multiple myeloma, Hodgkin's lymphoma and some metastasizing solid tumors (breast cancer, prostate cancer , non-small cell lung cancer).

  • 2. Myelofibrosis with non-tumor disease: Padget's disease, secondary hyperparathyroidism with vitamin D deficiency or renal osteodystrophy, SLE, less common systemic connective tissue diseases, tuberculosis, syphilis, chronic benzene poisoning.


  • Treatment of idiopathic myelofibrosis



    In addition to allo-HCT treatment should be palliative and does not continue life expectancy. The choice of therapy depends on the estimated life expectancy, estimated using the prognostic classification of DIPSS plus, used in both diagnosis and the course of the disease (8 risk factors: age> 65 years, general symptoms, Hb 25000 /μL, percentage of circulating blasts? 1 %, dependence on transfusions of erythromass, thrombocytopenia <100 000 /мкл, неблагоприятный кариотип). Бессимптомных пациентов из группы низкого или среднего риска 1 (0 или 1 из вышеперечисленных факторов) можно оставить без лечения. В случае возникновения симптомов возможно симптоматическое лечение. У пациентов с посредственным 2 или высоким риском (?2 из вышеперечисленных факторов риска) применяют allo-HCT или лекарства, которые проходят клинические испытания (ингибиторы JAK), при отсутствии такой возможности — симптоматическое лечение.

  • 1. Allo-HCT: the only method that gives a chance to completely cure the patient is recommended for patients with a presumed lifetime of <5 лет (группа высокого или среднего риска 2), зависимых от трансфузий эритромассы и с неблагоприятными цитогенетическими аберрациями. Процент 5-летней выживаемости после миелобляцийнои allo-HCT, рекомендованной пациентам до 45 лет, составляет ?45-50%.

  • 2. Cytoreductive therapy: (in smaller doses , than in other myeloproliferative tumors): it is indicated for patients with leukocytosis, thrombocytosis with clinical symptoms, significant splenomegaly and with severe general symptoms. It is used by hydroxy-secreting (first-choice drug), melphalan, busulfan, cladribine or IFN-?

  • 3. Treatment of anemia (Hb <10 г /дл): стимуляторы эритропоэза, андрогены (даназол, тестостерона енантан, флуоксиместерон), ГК (преднизолон), талидомид, леналидомид (у пациентов с делецией 5q-).

  • 4. Splenectomy: shown with a significantly enlarged /painful spleen, resistant to cytoreductive treatment of hemolytic anemia, depending on transfusion of erythromass, portal hypertension with a wedge physical symptoms. Mortality rate 5-10%.

  • 5. Irradiation of the spleen: shows are the same as for splenectomy, in addition, treatment of pain in spleen infarction.

  • 6. Irradiation of symptomatic foci of hematopoiesis outside the bone marrow.

  • 7. JAK inhibitors (eg, Русосолитиниб): in patients with clinically significant splenomegaly and severe general symptoms resistant to cytoreductive treatment.

  • 8. Transfusion of erythromass: little effective due to hypersplenism.


  • MONITORING

    A general blood test every 2-3 months.

    FORECAST

    The most unfavorable among all myeloproliferative diseases. The average survival time depends on the risk group: from 15.4 years in the low-risk group to 1.3 years in the high-risk group. Most patients die of infection, bleeding, or transformation into leukemia.