16-17. Leykemii.pptx

LEUKEMIA
lecture for 4th year students
Onichshenko V.O.

General information about
hematopoiesis
• Central organs of hematopoiesis:
-Bone marrow (localization - spongy substance of cancellous and flat
bones, as well as diaphyses of tubular bones)
In the red bone marrow there are all stages of maturation of
erythrocytes, granulocytes, monocytes, platelets, B-lymphocytes, as
well as the formation of precursors of T-lymphocytes.
-Thymus (localization - behind the sternum)
In the thymus, the maturation of T-lymphocytes is completed and their
proliferation takes place.

Peripheral hematopoietic organs:
- lymphoid formations of mucous membranes,
- lymph nodes,
- spleen
In the peripheral organs of hematopoiesis is the generation of an
immune response to contact of lymphocytes with the antigen

• Myelopoiesis - the formation of all formed elements of blood, except
lymphocytes
• Lymphopoiesis - the formation of lymphocytes (B- and T-cells).
According to the number of formed blood elements, there are 6
directions of myelopoiesis and 2 directions of lymphopoiesis
• In each of the directions of differentiation is allocated 6 classes of
cells:
• Class I - polypotent stem cells - can reproduce indefinitely
(proliferate), differentiate, giving rise to all the formed elements of the
blood;
90% of stem cells in the bone marrow are at rest and only 10% of these
cells are actively dividing and provide normal hematopoiesis.

• Class II - partially determined polypotent cells - precursors of
myelopoiesis and cells - precursors of lymphopoiesis, which can
be differentiated in two or more directions; sensitive to regulators
of myelopoiesis - erythropoietin, leukopoietin, thrombopoietin.
• Class III - unipotent cells can proliferate and differentiate in only
one direction; differentiation of lymphoid cells is aimed at the
formation of T- and B-lymphocytes; cell - the precursor of
myelopoiesis is differentiated in two directions:
1) precursor cell of granulocyto- and monocytopoiesis and
2) precursor cell of erythrocyto- and megakaryopoiesis.
Cells of the first - third classes are not morphologically
identified - they are undifferentiated blasts

• Class IV - blasts that are morphologically identifiable
(differentiated blasts) are the cells of each hematopoietic
sprout (lymphoblasts, plasmoblasts, monoblasts, myeloblasts,
erythroblasts, megakaryoblasts)
• Class V - maturing cells are represented by several
intermediate forms; each intermediate form can be
morphologically identified
• Class VI - mature cells with a limited lifespan, have specific
functions

• All tumors of hematopoietic tissue are denoted by the term
hemoblastosis, they are divided into two major groups:
• Myeloid tumors (21 species)
• 2) Lymphoid tumors:
• a) B-cell origin (15 species);
• b) T-cell origin (14 species)

According to the localization of the primary focus of
the tumor is divided into:
• 1. Leukemia (leukemia) - tumors with primary localization in the bone marrow.
• a) acute;
• b) chronic
• 2. Lymphomas - tumors with primary localization outside the bone marrow.
• a) lymphogranulomatosis (Hodgkin's lymphoma);
• b) non-Hodgkin's lymphoma

•1. In acute leukemias, the substrate of the
tumor are blast cells.
•2. In chronic leukemia, the tumor
substrate is maturing (5 cells) and mature
cells (6 cells).

Theories of leukogenesis
• Genetic - genetic defects and chromosomal
abnormalities
• Ionizing radiation - radiation therapy; man-made
disasters at nuclear power plants
• Chemical - benzene, pesticides, insecticides, tobacco
smoke; paints, solvents containing chlorine;
medicines (chlorambucil, cyclophosphamide, etc.)
• Viral: Epstein-Barr virus; HTLV retrovirus.

Pathogenesis of leukemias (clone theory)
•cell mutation
• weakening of immune defense mechanisms
•uncontrolled proliferation of mutated cells →
clone of leukemic cells
•malignancy of the process - the formation of new
daughter clones

Acute leukemia
•Acute leukemia is a malignant tumor of
hematopoietic tissue that primarily occurs in the
bone marrow and the morphological substrate of
which are immature blast cells -
undifferentiated or poorly differentiated
•The offspring of the mutated cell lose the ability
to differentiate into mature blood cells.

Clinical manfistations
• Stages of the course
• I. initial;
• ІІ. developed (stage of severe clinical manifestations);
• III. remission;
• IV. terminal.
The initial stage
• The initial manifestations are nonspecific, assessed only
retrospectively.

Expanded stage The clinical picture can be presented in the
form of three leading syndromes:
1. Tumor intoxication syndrome.
- fever,
- weakness,
- sweating,
- ↓ efficiency,
- ↓ appetite,
- ↓ body weight (due to the destruction of blasts and
secretion of malignant BAS cells)

2.Tumor growth syndrome
• increase in leukemic cells in the bone marrow
(ossalgia, sternalgia) →
• the release of blasts into the peripheral blood -
myelemia →
• metastasis - leukemic proliferation -these are small
foci of hematopoiesis of leukemic cells, which are
formed in various organs and are manifested:
• a) enlargement of the liver, spleen, lymph nodes;
• b) lesions of other organs: lungs, myocardium,
stomach, skin, CNS (neuroleukemia)

3. Hematopoietic suppression syndrome
Leukemic cells, growing in the bone marrow, "displace"
the sprouts of normal hematopoiesis, which is manifested
by the appearance of syndromes:
• anemic (weakness, dizziness, shortness of breath,
tachycardia)
• hemorrhagic (hemorrhages on the skin and mucous
membranes of the mouth, tonsils, conjunctiva
nosebleeds, gingival, uterine, gastrointestinal,
hemorrhages in the brain)
• immunodeficiency (ulcerative necrotic tonsillitis,
stomatitis, pneumonia, furunculosis, paraproctitis)

III. Remission
1. Complete clinical and hematological remission is:
Normalization of clinical symptoms (not less than 1 month)
2. Normalization of the composition of peripheral blood
3. In the bone marrow, the number of blast cells does not
exceed 5%
Complete clinical and hematological remission lasting
more than 5 years is regarded as recovery.

•IV. Terminal stage
-is the final stage,
-characterized by resistance to
chemotherapy

Diagnosis of Acute leucemia
• General blood analysis:
- Leukocytes from 1.0 × 10 9 / l to 200 × 10 9 / l
- blast cells;
- leukemic "abyss" - the absence of maturing cells - V class
(there are blasts and mature cells of class VI)
-may be anemia, thrombocytopenia, ↑ ESR
• Sternal puncture: blasts> 30%
• Trepanobiopsy of the iliac bone (histological examination
of the stroma and islets of hematopoiesis).

Cytochemical and immunophenotypic studies
allow to differentiate variants of acute leukemia.
At cytochemical research:
a) acute lymphoblastic leukemia is characterized
by a positive reaction to glycogen,
b) for acute myeloblastic leukemia - a positive
reaction to myeloperoxidase.
Immunophenotypic studies - antigens detected
on the surface of blasts by groups of antibodies,
combined into clusters of differentiation

• Molecular genetic studies allow to identify individual genes
and their products - regulatory oncogenes and other proteins
(ie changes in the genome responsible for the malignant
transformation of hematopoietic cells)
• Cytogenetic analysis reveals chromosomal abnormalities.
• Instrumental studies in acute leukemia:
- Radiography and tomography of the lungs
- ECG
- Ultrasound
- Radioisotope scan of the liver
- Spinal tap: detection of blasts cells in neuroleukemia

Index Result Reference ranges
Leucocytes 97 4.0-9.0 х109/L
Hemoglobin 59 M: 130-160 g/L
F:120-140 g/L
Red blood cells 1.8 M: 4,0 – 5,0 х1012/L
F:3.7- 4.7 х1012/L
Color index 1.0 0.85-1.05
Reticulocytes 0.6 0.5-1.0 %
Middle cell volume (MCV) 89.1 81-99 mkm3
Middle concentration
hemoglobin (MCH)
32.6 27.0-36.0 pg
hemoglobin in cells (MCHC)
32. 32.0-36.0 g/dl
Hematocrit 32 M.43-54%
F.36-47%
Platelets 18 150-390 х109/L
ESR 53 M: < 10
F: < 15 mm/h
Index Result % Normal range % Absolute range Normal
Eosinophils 5 0,5 – 5,0 4,85 0-0.5 х109/л
Basophils 0 0-1 0 0-0.2 х109/л
Blasts 67 0 67 0
Mielocytes 0 0 0 0
Metamielocytes 0 0 0 0
Ban cells 0 0 0 0.1-0.6 х109/л
Segment-Nuclear
neutrophils
16 0 15.52 2.0-7.2 х109/л
Lymphocytes 7 19.40 1,6 1.2-3.2 х109/л
LEUCOCYTES FORMULA
A decrease in the level of erythrocytes, platelets, an
increased content of leukocytes, a normal color indicator
and a level of reticulocytes. In the leukocyte formula,
there are blast cells and a leukemic gap (absence of
maturing forms between blasts and mature cells -
promyelocytes, myelocytes, metamyelocytes). Such
changes indicate normochromic normoregenerative
anemia, and changes in the blood formula are
characteristic of acute leukemia. According to peripheral
blood data, it is impossible to establish the morphological
variant (lymphoid or myeloid).

Leucocytes 108.4 4.0-9.0 х109/L
F:120-140 g/L
F:3.7- 4.7 х1012/L
Middle cell volume (MCV) 84 81-99 mkm3
hemoglobin (MCH)
38 27.0-36.0 pg
32 32.0-36.0 g/dl
F.36-47%
ESR 61 M: < 10
F: < 15 mm/h
A decrease in the level of erythrocytes, platelets, an increased content of
leukocytes, a normal color indicator and a level of reticulocytes. In the
leukocyte formula, there are blast cells and a leukemic gap (absence of
maturing forms between blasts and mature cells - promyelocytes,
myelocytes, metamyelocytes). Such changes indicate normochromic
normoregenerative anemia, and changes in the blood formula are
characteristic of acute leukemia. According to peripheral blood data, its
morphological variant (lymphoid or myeloid) cannot be established
Eosinophils 1 0,5 – 5,0 1,08 0-0.5 х109/л
Basophils 0 0-1 0 0-0.2 х109/л
Blasts 62 0 67.21 0
Promielocytes 0 0 0 0
Mielocytes 0 0 0 0
Ban cells 2 1-6 2,17 0.1-0.6 х109/л
Segment-Nuclear
neutrophils
21 50-70 22,76 2.0-7.2 х109/л
Lymphocytes 11 19-40 11,92 1.2-3.2 х109/л
Monocytes 3 3-10 3,25 0.3-0.8 х109/л
LEUCOCYTES FORMULA

Index Result % Reference ranges %
Blasts 49,0 <5.5
Promielocytes 0 1.0-4.1
Mielocytes 0 7.0-12.2
Metamielocytes 0,5 8.0-15.0
Ban cells 2,5 12.8-23.7
Segment-Nuclear neutrophils 11,5 13.1-24.1
Eosinophils 2,0 0.5-5.8
Basophils 0 0-0.5
Lymphocytes 10,25 4.3-13.7
Monocytes 3,0 0.7-3.1
Plasma cells 1,5 0.1-1.8
Erythroblasts 0 0,2-1,1
Pronormocytes 0,25 0,1-1,2
Normocytes
-basophilic
-polichromatophilic
-oxiphilic
1,5
14,5
3,5
1,4-4,6
8,9-16,9
0,8-5,6
Leuco-erythroid ratio 4,1:1 3-4:1
Myelogram
In the myelogram, the content of blast cells is more than the norm and exceeds 30%.
Such changes are observed in malignant diseases of the hematopoietic system - acute
leukemias, both lymphoid and myeloid. According to the results of the myelogram, it is
impossible to establish the morphological variant of leukemia.

Methods of treatment of hematooncological patients
• Cytostatic therapy It consists of the following stages:
- Induction of remission (4-6 weeks).
- Consolidation (consolidation of remission) - 6 weeks.
- Maintenance therapy - alternates with cycles of consolidation in
1 month.
- Treatment of relapse.
Unified standardized programs for the treatment of acute
leukemia have been developed. Several chemotherapeutics with
different mechanisms of action are prescribed, which affect
different phases of mitosis of a leukemic blast cell and disrupt the
structure of its DNA.

• Cytostatic therapy for acute lymphoblastic leukemia:
1. Induction of remission:
Vincristine, prednisolone, L-asparaginase, doxorubicin
2. Supportive therapy:
Mercaptopurine, methotrexate
• Cytostatic therapy for acute myeloblastic leukemia
4. Induction of remission:
• Cytarabine, doxorubicin
Supportive therapy:• Cytarabine, cyclophosphamide
The treatment of anemia, thrombocytopenia, infectious
complications, detoxification therapy.

• 2. Radiation therapy
• 3. Stem cell transplantation (SCT) has been used since
the 1960s. In 1989, the first transplant of umbilical
cord blood to a child.
Peripheral blood SCT has been performed since the
1990s.
Autologous SCT - replantation of own bone marrow
Syngenna SCT - identical phenotype (homozygous)
identical twins
Allogeneic SCT- from a donor (usually a relative)

CHRONIC MYELOLEUKEMIA it is a
form of leukemia in which there is increased
education granulocytes, which are the
substrate of the tumor
The source of the tumor is a precursor cell of myelopoiesis. In
90-97% of patients with CML chromosomal abnormality of 22
pairs (Philadelphia Ph-chromosome) in the cells of the
granulocyte, erythroid, monocyte and platelet series.

• Clinical variants of CML:
- typical CML (Ph+)
- atypical CML (Ph-)
- CML in children
• MORPHOLOGICAL OPTIONS of CML:
- Chronic eosinophilic leukemia;
- Chronic basophilic leukemia;
- Chronic monocytic leukemia;
- Chronic neutrophilic leukemia.
• PHASES OF THE CLINICAL COURSE:
- chronic progressive (acceleration)
- acute (blast crisis)
• Stages:
- Initial;
- Expanded;
- terminal

Clinic
• Asthenic syndrome: weakness, malaise
• Discomfort in the epigastric region, left and right hypochondrium
• Enlargement of the spleen
• Thrombohemorrhagic manifestations
• Anemic syndrome
• Osteoporosis

Diagnosis of chronic myelogenous leukemia:
1.Enlarged spleen
2. General blood analysis :
- leukocytosis
- shift of the formula to the left - all maturing forms of the
granulocyte series: metamyelocyte, myelocyte, promyelocyte,
- basophilic-eosinophilic association;
3. Bone marrow - myeloid metaplasia.
Leukemoid reaction - a shift of the formula to the left (all
maturing forms of the granulocyte series),but there is no
basophilic-eosinophilic association.

Leucocytes 28.9 4.0-9.0 х109/L
F:120-140 g/L
F:3.7- 4.7 х1012/L
hemoglobin(MCH)
29.3 27.0-36.0 pg
32.8 32.0-36.0 g/dl
F.36-47%
Platelets 228 150-390 х109/L
ESR 40 M: < 10
F: < 15 mm/h
Eosinophils 7.0 0,5 – 5,0 2,02 0-0.5 х109/л
Basophils 4.0 0-1 1,16 0-0.2 х109/л
Blasts 0 0 0 0
Promielocytes 1 0 0,29 0
Mielocytes 4 0 1,16 0
Metamielocytes 7 0 2,02 0
Ban cells 11 1-6 3,18 0.1-0.6 х109/л
Segment-Nuclear
neutrophils
52 50-70 15,03 2.0-7.2 х109/л
Lymphocytes 12 19-40 3,47 1.2-3.2 х109/л
LEUCOCYTES FORMULA
A blood test shows a decrease in hemoglobin and an increase
in the level of leukocytes. The leukocyte formula contains
maturing cells - promyelocytes, myelocytes, metamyelocytes
(shift of the formula to the left) and basophilic-eosinophilic
association (increased content of eosinophils and
basophils). Such changes occur in chronic myeloid
leukemia.

Leucocytes 180.0 4.0-9.0 х109/L
F:120-140 g/L
F:3.7- 4.7 х1012/L
Middle cell volume (MCV) 87.4 81-99 mkm3
hemoglobin
(MCH)
36 27.0-36.0 pg
35 32.0-36.0 g/dl
F.36-47%
Platelets 473 150-390 х109/L
ESR 31 M: < 10
F: < 15 mm/h
Eosinophils 9 0,5 – 5,0 16,20 0-0.5 х109/л
Basophils 5 0-1 9,00 0-0.2 х109/л
Blasts 8 0 14,40 0
Promielocytes 8 0 14,40 0
Mielocytes 7 0 12,60 0
Metamielocytes 14 0 25,20 0
Ban cells 18 1-6 32,40 0.1-0.6 х109/л
Segment-Nuclear
neutrophils
23 50-70 41,40 2.0-7.2 х109/л
Lymphocytes 8 19-40 14,40 1.2-3.2 х109/л
LEUCOCYTES FORMULA
A blood test shows a decrease in hemoglobin and an
increase in the level of leukocytes. In the leukocyte
formula, there are blasts and maturing cells -
promyelocytes, myelocytes, metamyelocytes (shift of the
formula to the left) and basophilic-eosinophilic
association (increased content of eosinophils and
basophils). Such changes occur in chronic myeloid
leukemia.

Blasts 0 <5.5
Promielocytes 0,5 1.0-4.1
Mielocytes 4,5 7.0-12.2
Metamielocytes 1,0 8.0-15.0
Ban cells 5,0 12.8-23.7
Segment-Nuclear neutrophils 7,5 13.1-24.1
Eosinophils 2,5 0.5-5.8
Basophils 1,0 0-0.5
Lymphocytes 6,0 4.3-13.7
Monocytes 0,5 0.7-3.1
Plasma cells 69,0 0.1-1.8
Pronormocytes 0 0,1-1,2
Normocytes
-basophilic
-polichromatophilic
-oxiphilic
0,5
0,5
1,5
1,4-4,6
8,9-16,9
0,8-5,6
Leuco-erythroid ratio 39:1 3-4:1
In the myelogram, the number of blast cells does not exceed the
norm. The content of plasma cells is more than 15%. The
patient has a chronic myeloproliferative process, for example,
chronic myeloid leukemia.

Treatment
1. Tyrosine kinase inhibitors (TKIs) continued:
1) imatinib 400 mg once a day p/o;
2) dasatinib 100 mg once daily p/o is effective in all cases of imatinib
resistance caused by BCR-ABL1 gene mutations;
3) nilotinib 300 mg (400 mg in second-line therapy) 2 × a day p/o is
effective in all cases of imatinib resistance caused by BCR-ABL gene
mutations;
4) bosutinib 500 mg once a day p/o;
5) ponatinib 45 mg once a day p/o.

2. Allogeneic Stem cell transplantation (SCT) : feasibility can be
considered in patients who have been selected for this procedure (in the
absence of access to ponatinib), or if the treatment of ≥2 TKIs was
ineffective and/or their intolerance was observed.
3. Interferon-α is used in pregnant women (monotherapy), in patients
who are not candidates for Allogeneic Stem cell transplantation (SCT),
after the ineffectiveness of treatment with tyrosine kinase inhibitors
4. Hydroxyurea is used short-term for the purpose of cytoreduction
before confirming the diagnosis, or as palliative therapy in individual
patients.

•CHRONIC LYMPHOLEUKEMIA
- leukemia, in which there is increased
formation of morphologically mature
lymphocytes, which are the substrate of
the tumor.

Clinic
• At the time of diagnosis, more than half of patients have no clinical symptoms
(only lymphocytosis is detected during a routine examination of blood
morphology).
1. Subjective manifestations: nonspecific symptoms — loss of body weight by ≥10%
in the last 6 months, fever (>38 °C) lasting ≥2 weeks. (without co-infection),
increased sweating, especially at night, without co-infection lasting >2 weeks,
significant general weakness, increased fatigue, abdominal heaviness and
abdominal pain (symptoms associated with splenomegaly).
2. Objective symptoms: increase in lymph nodes (in 50–90%), spleen (in 25–55%),
liver (in 15–25%), other lymphoid organs (Waldeyer rings, tonsils); damage to
extralymphatic organs (most often the skin, in <5%), dryness of the mucous
membrane of the mouth and eyes, due to lymphoid infiltration of the parotid and
lacrimal glands (Mikulych's symptom)
3. Complications: infections and autoimmune cytopenias, especially autoimmune
hemolytic anemia and immune thrombocytopenia.

DIAGNOTIC
1) leukocytosis
2) lymphocytosis 60-80-90%;
3) the shadows of Botkin – Gumprecht (half-
destroyed nuclei of defective lymphocytes crushed
during the preparation of a blood smear);
Bone marrow - lymphocytes more than 30%.

In the blood test, there is a decrease in the content of
hemoglobin, erythrocytes, platelets, an increase in the level
of leukocytes and platelets, as well as lymphocytes in
percentages and absolute numbers. Such changes can
occur with chronic lymphoid leukemia or with metastasis
of a lymphoid tumor, for example, lymphoma, in the bone
marrow.
LEUCOCYTES FORMULA
Leucocytes 124.0 4.0-9.0 х109/L
F:120-140 g/L
F:3.7- 4.7 х1012/L
Color index 0.87 0.85-1.05
hemoglobin
(MCH)
29.3 27.0-36.0 pg
35.1 32.0-36.0 g/dl
F.36-47%
ESR 44 M: < 10
F: < 15 mm/h
Eosinophils 2 0,5 – 5,0 2,48 0-0.5 х109/л
Basophils 0 0-1 0 0-0.2 х109/л
Blasts 0 0 0 0
Mielocytes 0 0 0 0
Ban cells 1 1-6 1,24 0.1-0.6 х109/л
Segment-Nuclear
neutrophils
5 50-70 6,20 2.0-7.2 х109/л
Lymphocytes 92 19-40 114,08 1.2-3.2 х109/л

Leucocytes 24.0 4.0-9.0 х109/L
F:120-140 g/L
F:3.7- 4.7 х1012/L
hemoglobin
(MCH)
29.5 27.0-36.0 pg
33.6 32.0-36.0 g/dl
F.36-47%
Platelets 210 150-390 х109/L
ESR 14 M: < 10
F: < 15 mm/h
Eosinophils 4 0,5 – 5,0 0,96 0-0.5 х109/л
Basophils 0 0-1 0 0-0.2 х109/л
Blasts 0 0 0 0
Mielocytes 0 0 0 0
Ban cells 3 1-6 0,72 0.1-0.6 х109/л
Segment-Nuclear
neutrophils
16 50-70 3,84 2.0-7.2 х109/л
Lymphocytes 72 19-40 17,28 1.2-3.2 х109/л
LEUCOCYTES FORMULA
In the blood test, there is an increase in the level of leukocytes, as well as
lymphocytes in percentages and absolute numbers. Such changes can
occur with chronic lymphoid leukemia or with metastasis of a lymphoid
tumor, for example, lymphoma, in the bone marrow.

Blasts 0 <5.5
Promielocytes 0 1.0-4.1
Mielocytes 0.5 7.0-12.2
Metamielocytes 1.0 8.0-15.0
Ban cells 0.5 12.8-23.7
Segment-Nuclear neutrophils 0 13.1-24.1
Eosinophils 0 0.5-5.8
Basophils 0 0-0.5
Lymphocytes 93.5 4.3-13.7
Monocytes 0 0.7-3.1
Plasma cells 0 0.1-1.8
Pronormocytes 0 0,1-1,2
Normocytes
-basophilic
-polichromatophilic
-oxiphilic
1,5
2,5
0,5
1,4-4,6
8,9-16,9
0,8-5,6
Leuco-erythroid ratio 21,2:1
The content of blast cells does not exceed 30%, which excludes acute
leukemia. There is significant lymphocytosis. The patient has a chronic
lymphoproliferative process, possibly chronic lymphoid leukemia or
metastases of a lymphoid tumor, such as lymphoma, in the bone
marrow.

First line treatment
• purine analogues (fludarabine, cladribine, pentostatin) in monotherapy or
in combined schemes - FCR cycle [fludarabine, cyclophosphamide,
rituximab]
or
• CCR [cladribine, cyclophosphamide, rituximab] every 28 days, chlorambucil
in combination with an anti-CD20 antibody (rituximab, obinutuzumab,
ofatumumab)
or
• bendamustine in combination with rituximab

Treatment in case of relapse or failure of first-
line treatment
1) relapse or progression after 12–24 months. from the end of monotherapy or 24–
36 months. after completion of immunochemotherapy → repeat first-line
treatment;
2) relapse or progression after a shorter period → choose a different treatment
tactic than before:
• purine analogues in combination with cyclophosphamide and rituximab,
• bendamustine in monotherapy or in combination with rituximab (BR) or
ofatumumab,
• alemtuzumab in monotherapy or in combination with a purine analogue or
rituximab,
• high doses of methylprednisolone in monotherapy or in combination with
rituximab (in patients with resistance to purine analogs),
• tyrosine kinase inhibitors (ibrutinib or idelalisib in combination with rituximab)

Supportive therapy
1. Prevention of infections: vaccination against influenza, pneumococci and
Haemophilus influenzae type B;
- acyclovir and cotrimoxazole in patients treated with purine analogues,
idelalisib or alemtuzumab;
- in patients with hypogammaglobulinemia (<500 mg/dL) with recurrent
infections of the respiratory system, which require the appointment of
intravenous antibiotic therapy and/or hospitalization of subcutaneous
immunoglobulin.
2. Treatment of autoimmune cytopenias:
- glucocorticosteroids;
- second-line treatment — splenectomy, IVIG, immunosuppressive drugs,
rituximab

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