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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3063_Библиотеки_им_академика_М_И_Перельмана
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Assessment
The initial presentation of the patient is consistent with stroke syndrome. Given her platelet
count and recent history of bleeding, a hemorrhagic stroke appears more likely.
Pancytopenia occurs with any primary cancer of the marrow, such as leukemia or any
metastatic cancer that invades the marrow. Infections such as tuberculosis can also rarely cause
a pancytopenia if they invade the marrow as well. Vitamin B12 and folate deficiency also
rarely cause a pancytopenia, but they are not associated with disseminated intravascular
coagulation, such as this patient has. The same is true of splenic sequestration and systemic
lupus erythematous. None of the causes of pancytopenia gives blasts on the peripheral smear,
except for acute leukemia. The leukemia most commonly associated with disseminated
intravascular coagulation is M3, or promyelocytic leukemia.
The most dangerous thing to this patient now is bleeding from the low platelet count and
infection. Anyone with temp 38 and ANC <500 needs antibiotics within 60 minutes of it being
found. Pseudomonal coverage is very important, so the initial choice can be a carbapenem
(meropenem or imipenem), a synthetic penicillin such as piperacillin/tazobactam, or an anti-
pseudomonal cephalosporin such as cefepime.
Differential/ANC: 20% of 1,500 WBC or ANC 300
PT, aPTT: 18 seconds, 78 seconds (elevated)
D-dimers, fibrin split products: increased
Fibrinogen decreased
Head CT: left intraparenchymal hemorrhage in parietal lobe
Mechanism of AML: defect occurs shortly after the commitment of the stem cell to the
myeloid line
Stem cells are CD34+
Definitive diagnosis is by flow cytometry: “CD” means “cluster of differentiation”
361
Basic Science Correlate
Mechanism of DIC in M3 promyelocytic leukemia: Release of azurophilic granules
from promyelocytes that activate the clotting cascade
CCS NOTE
Once the clock is moved forward, nothing can be done to move it back. You can only
go forward in time, even “simulated” time.
Further Management Plan/Results
Diffuse infiltration with monomorphic
population of abnormal promyelocytes.
Decreased megakaryocytes.
15:17 translocation is present
Discussion
Bone marrow biopsy
1.
Cytogenetic studies; FISH test for 5q
deletion, 15:17 translocation
2.
Add vancomycin, linezolid or daptomycin if
still febrile after 48–72 hours
3.
362
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Acute myeloid leukemia is the most common acute leukemia of adults. Its incidence increases
with age and is associated with previous radiation exposure, exposure to alkylating agents,
benzene, and prior history of myelodysplasia. It is divided into seven morphologic types,
including undifferentiated (M0), promyelocytic (M3), monocytic (M5), erythroleukemia (M6),
and megakaryoblastic (M7). Undifferentiated forms may be difficult to discern from acute
lymphocytic leukemia, but surface markers suggest myeloid origin. The presence of Auer rods
or myeloperoxidase indicates myeloid origin of the cells.
Patients may present with high WBC. If WBC >150,000/mm
3
, patients may experience
complications of leukostasis, which include diffuse CNS changes caused by sludging or
hemorrhage, blurry vision, and respiratory decompensation. Leukostasis can be treated with
leukapheresis or cytoreduction with urgent hydroxyurea or chemotherapy administration.
Patients may also present with low WBC counts. Monocytic disease may present with CNS,
gum, or skin infiltration. Megakaryoblastic disease is characterized by marked marrow
fibrosis.
Acute promyelocytic leukemia is a distinct form of acute myeloid leukemia and has the best
prognosis among AML subtypes. It is caused by a translocation between the retinoic acid
receptor and the PML gene (translocation 15:17). Acute promyelocytic leukemia cells contain
procoagulant material that, when it gains access to the circulation, may initiate disseminated
intravascular coagulation. Patients often present with complications of acute bleeding.
Treatment of acute promyelocytic leukemia has consisted of an induction regimen of an
anthracycline such as daunorubicin or idarubicin, plus cytosine arabinoside. Many early deaths
were a result of disseminated intravascular coagulation-related problems and were often
exacerbated by cell lysis in the setting of treatment. Another form of therapy is all-trans
retinoic acid; when exposed to this agent, it seems that acute promyelocytic leukemia cells
undergo maturation. This may help to avoid problems seen with cell lysis during initiation of
treatment.
363
The prognosis of acute promyelocytic leukemia is slightly better than it is with other forms of
acute myeloid leukemia. In general, long-term survival with acute myeloid leukemia is
approximately 40% without transplant.
Basic Science Correlate
The most important prognostic indicator is cytogenetic abnormalities on flow
cytometery or bone marrow biopsy (PML/RARA—15;17).
Why doesn’t combining beta lactam antibiotics increase efficacy? Penicillins,
carbapenems, aztreonam, and cephalosporins all inhibit the cell wall. One mechanism
= NO synergy.
Why are echinocandins (e.g., caspofungin) so safe? Their mechanism, inhibiting 1,3
glucan linkages in fungi, does not exist in human cells.
What is the mechanism of daptomycin failure in pneumonia? Inactivation by
surfactant
CLINICAL PEARL
Acute myeloblastic leukemia
Clinically: usually bleeding diathesis, infections, and anemia
WBC may be increased, normal, or low
364
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Follow-up Management and Prevention
Final Diagnosis
Acute myeloblastic leukemia/acute promyelocytic leukemia/disseminated intravascular
coagulation
Blasts ≥20% in marrow or peripheral blood
Blasts: high cytoplasm-to-nucleus ratio, azurophilic granules, Auer rods
Cytogenetics and cell markers consistent with myeloblasts
Stabilize the CNS bleed with platelet transfusions
Treatment with cytosine arabinoside (ARA-C) and daunorubicin or idarubicin
All-trans-retinoic acid (ATRA) is added just for M3 promyelocytic leukemia
Add voriconazole or caspofungin if still febrile 2-3 days after addition of vancomycin
Allogenic bone-marrow transplantation in those with high-risk disease or those who relapse
after induction chemotherapy
365
Case 2
Chief Complaint
Fatigue
History and Physical Examination
A 75-year-old man comes to the office because of progressive fatigue over the last 3
months, as well as several episodes of upper respiratory infection over the last year. He
also feels “fullness” in his abdomen and states that his appetite has deteriorated, although
he has not lost any weight. He denies chronic fevers, chills, cough, and a history of
abnormal bleeding.
Physical examination shows bilateral adenopathy in the cervical and supraclavicular
chain. The lymph nodes are hard and nontender; the largest is approximately 3 cm. The
chest is clear and the heart has a RRR with normal S1 and S2. The abdomen is soft and
nontender; a splenic edge is palpated 5 cm below left costal margin, and bilateral inguinal
adenopathy is present. Rectal examination is negative for fecal occult blood.
Differential Diagnosis
Chronic lymphocytic leukemia
1.
Chronic myeloid leukemia
2.
Hodgkin’s or non-Hodgkin’s lymphoma
3.
Infectious mononucleosis
4.
Cytomegalovirus infection
5.
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Initial Management
Setting: outpatient
Diagnostic/Therapeutic Plan
Test Results
Assessment
The patient presents with diffuse lymphadenopathy, splenomegaly, and a history of fatigue and
frequent infections. A primary malignancy of the lymphocytes needs to be excluded.
CCS NOTE
Normal lab values are routinely provided with test results on CCS.
CBC
Differential
Chest x-ray
BUN/creatinine
Heterophile antibodies (monospot test)
WBCs 75,000/mm
3
(normal 4,000–11,000/mm
3
), hemoglobin 10 mg/dL (normal: 13–17
mg/dL), platelets 70,000/mm
3
(normal 150,000–400,000/mm
3
)
80% mature lymphocytes, 15% granulocytes, 5% monocytes
Chest x-ray normal
BUN/creatinine 20 mg/dL, 1.0 mg/dL
Negative monospot and CMV antibodies
367
The subacute presentation here is more consistent with a lymphoma or chronic leukemia rather
than acute leukemia. Infectious etiologies causing generalized adenopathy and splenomegaly
include cytomegalovirus and Epstein-Barr virus-related illness. The thrombocytopenia and
hemolytic anemia are likely autoimmune in nature and related to the primary disease.
Further Management Plan/Results
Diffuse infiltration with mature-appearing
lymphocytes (10% of total); myeloid and
erythroid maturation appear normal; increased
numbers of megakaryocytes are seen
Positive
No lymphoma
Positive for CD5 and CD20
Normal
Discussion
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia primarily involving
people age >50. It accounts for 30% of leukemia. It is not associated with prior exposure to
radiation or chemicals.
Bone marrow biopsy
1.
Direct Coombs test
2.
Lymph node biopsy
3.
Flow cytometry of peripheral blood
4.
Cytogenetics
5.
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The disease is characterized by prominent peripheral lymphocytosis of mature-appearing
lymphocytes of B-cell lineage. These cells typically infiltrate the lymph nodes diffusely, the
spleen, and the bone marrow. In some the disease may be indolent and detected coincidentally
on routine blood work. In others it can progress more rapidly.
Patients may present with history of recurrent infections. Often they have a decrease in cell-
mediated immunity. Hypogammaglobulinemia is common.
Patients with CLL may develop autoimmune antibodies to hematopoietic cells. Autoimmune
hemolytic anemia occurs in approximately 15% of cases. Immune-based thrombocytopenia and
granulocytopenia also occur. Several staging systems exist, most notably the Rai and Binet
systems. In Rai system:
Low-risk disease is associated with survival >10 yrs, whereas high-risk disease is associated
with survival <5 yrs. Like most chronic hematologic malignancies, patients can go into
remission for long periods of time with treatment, but curing the disease is difficult.
Unless symptomatic with extensive fevers, chills, sweats, recurrent infections, or profoundly
anemic, neutropenic or thrombocytopenic, patients are observed over time. When treatment is
needed, the standard of care is fludarabine/cyclophosphamide/rituximab (FCR) in younger, fit
patients, and bendamustine/rituximab (B/R) in less-fit or older patients. Indications for
treatment include:
Low-risk: patients with lymphocytosis alone (stage 0)
Intermediate risk: patients with lymphadenopathy (stage 1) or splenomegaly (stage 2)
High risk: patients with anemia and thrombocytopenia (stage 3 or 4)
Systemic symptoms
Bone marrow failure
Autoimmune manifestations
369
There is no clear evidence that a single specific therapy is more effective than any other.
Prednisone is sometimes added in the presence of autoimmune manifestations, such as anemia
or thrombocytopenia.
Fludarabine can be used as a single agent or combined with an anti-CD20 agent such as
rituximab. Cyclophosphamide is often used.
The treatment of CLL may look like the treatment of non-Hodgkin’s lymphoma, as CLL is really
a form of lymphoma that is circulating in the blood.
CLINICAL PEARL
Chronic lymphocytic leukemia
Follow-up Management and Prevention
Massive splenomegaly
Bulky lymph node disease
Recurrent infections
Clinically: usually asymptomatic, increased infections
WBCs increased with predominance of mature lymphocytes
Hemolytic anemia
Asymptomatic patients are stages 0 and 1; observe without chemotherapy
Symptomatic patients, those in advanced stages, or those with bone marrow failure
are stages 2, 3, and 4; treat with FCR (fludarabine, rituximab, and
cyclophosphamide) or bendamustine/rituximab (B/R).
370
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