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• Hyperleukocytosis : Refers to lab abnormality that has been variably defined as a total leukemia
blood cell count greater than 50,000/microL or 100,000/microL.
• Leukostasis : Aka Symptomatic Hyperleukocytosis
Most commonly seen in patients with AML or CML in blast crisis.
Characterized by an extremely elevated blast cell count and symptoms of decreased tissue
• Leucostasis is a Pathologic diagnosis white cell plugs are seen in the microvasculature.
• Clinically diagnosed empirically when a patient with leukemia and hyperleukocytosis presents
with respiratory or neurological distress.
• Prompt t/t is indicated since, if left untreated, the one-week mortality rate is approx. 20 to 40 pc.
• The frequency of hyperleukocytosis is 5–13% in AML and 10–30% in ALL.
• More common with myelomonocytic (FAB-M4) leukemia, monocytic (FAB-M5) leukemia, or
the microgranular variant of acute promyelocytic leukemia (FAB-M3) .
• Symptoms of leukostasis occur less frequently and typically affect pts with WBC counts over
100 x 109/L.
• The incidence appears to be highest in infants, patients between the ages of 10 and 20 years,
males, and those with a T cell phenotype
• Symptoms of leukostasis are rarely seen.
• TLS and DIC are more common complications related to the elevated WBC count.
• Symptoms of leukostasis are rare unless the WBC count exceeds 400 x 109/L.
• Pts. with CML typically present with leukocytosis and a median WBC count of approx. 100 x
• Symptoms of leukostasis are very uncommon in chronic phase but can be seen occ. in
patients with myeloid blast crisis and very elevated blast counts.
PATHOPHYSIOLOGY OF LEUKOSTASIS
• There are two main theories, which are not mutually exclusive:
Large population of leukemic blasts (less deformable than mature leukocytes) Increases blood
viscosity Plug microcirculation impede blood flow (leukostasis).
Worsened by RBC transfusions or the use of diuretics, both of which can increase whole
Local hypoxemia may be exacerbated by the high metabolic activity of the dividing blasts and the
associated production of various cytokines Endothelial damage.
• Primitive myeloid leukemic cell are capable of invading through the endothelium and causing
• Brain(40 pc ) and lung(30 pc) are most commonly affected.
• Pulmonary involvement
• Dyspnea and hypoxia with/out diffuse interstitial or alveolar infiltrates on imaging studies.
• Arterial PaO2 can be falsely decreased in pts. with hyperleukocytosis, since the WBCs in the
test tube utilize oxygen.
• Pulse oximetry provides a more accurate assessment of O2 saturation in this setting.
• Neurological involvement
• Visual changes, headache, dizziness, tinnitus, gait instability, confusion, somnolence, and,
• Increased risk of intracranial hemorrhage that persists for at least a week after the reduction
of white cell count, perhaps from a reperfusion injury as areas of the brain that were
ischemic from leukostasis regain blood flow.
• Approx. 80 pc. of pts. with leukostasis are febrile, which may be due to inflammation associated with
leukostasis or concurrent infection.
• Less common s/s of leukostasis include
• ECG evidence of myocardial ischemia or right ventricular overload,
• Worsening renal insufficiency,
• Acute limb ischemia, or
• Bowel infarction
• Pulse oximetry provides a more accurate assessment of O2 saturation.
• R/O Pseudo thrombocytosis : Manual counting
• R/O Pseudo hyperkalemia
• DIC occurs in up to 40 pc. of pts. : FDP and d-Dimer.
• Spontaneous TLS is present in up to 10 pc. of pts. with leucostasis : Uric acid, potassium,
phosphate, calcium and creatinine.
• For pts with symptomatic or asymptomatic hyperleukocytosis
• Initial t/t with induction chemotherapy rather than hydroxyurea or leukapheresis.
• Accompanied by TLS prophylaxis with aggressive hydration and allopurinol.
• For pts without symptoms of leukostasis who must have induction chemotherapy delayed
• Cytoreduction with hydroxyurea rather than leukapheresis.
• Cytoreduction with hydroxyurea can ppt. or exacerbate hyperuricemia and/or TLS IV
hydration and TLS prophylaxis.
• For pts with symptoms of leukostasis who must have induction chemotherapy delayed
• Initial cytoreduction with leukapheresis in combination with hydroxyurea to lower or stabilize
the WBC count.
• Treatment of the leukemia can result in pulmonary hemorrhage from lysis of blasts in the lung,
called leukemic cell lysis pneumopathy.
• When APML is treated with differentiating agents like tretinoin and arsenic trioxide
• Cerebral or pulmonary leukostasis may occur as tumor cells differentiate into mature
• This complication can be largely avoided by using cytotoxic chemotherapy or arsenic together
with the differentiating agents.
• MSCC is defined as compression of the spinal cord and/or cauda equina by an extradural tumor
• The minimum radiologic evidence for cord compression is indentation of the theca at the level of
• Spinal cord compression occurs in 5–10% of pts with cancer.
• Epidural tumor is the first manifestation of malignancy in about 10% of pts.
• Lung cancer is the most common cause of MSCC.
• Metastatic tumor involves the vertebral column more often than any other part of the bony
• Lung, breast, and prostate cancer are the most frequent offenders.
• Multiple myeloma also has a high incidence of spine involvement.
• Lymphomas, melanoma, renal cell cancer, and genitourinary cancers also cause cord
• The thoracic spine is the most common site (70%), followed by the lumbosacral spine (20%) and
the cervical spine (10%).
• Involvement of multiple sites is most frequent in patients with breast and prostate carcinoma.
• Direct extension of a paravertebral lesion through the intervertebral foramen : Lymphoma,
myeloma, or pediatric neoplasm.
• Parenchymal spinal cord metastasis due to hematogenous spread is rare.
• Intramedullary metastases can be seen in lung cancer, breast cancer, renal cancer, melanoma, and
• Obstruction of the epidural venous plexus leads to edema.
• Local production of inflammatory cytokines enhances blood flow and edema formation.
• Compression compromises blood flow, leading to ischemia.
• Production of vascular endothelial growth factor is associated with spinal cord hypoxia.
• Localized back pain and tenderness : MC presentation
• Involvement of vertebrae by tumor.
• Pain is usually present for days or months before other neurologic findings appear.
• Exacerbated by movement and by coughing or sneezing.
• Radicular pain : Less common
• Usually develops later.
• Radicular pain in the cervical or lumbosacral areas may be unilateral or bilateral.
• Radicular pain from the thoracic roots is often bilateral and is described by pts as a feeling of
tight, band-like constriction around the thorax and abdomen.
• Lhermitte’s sign
• Loss of bowel or bladder control may be the presenting symptom but usually occurs late in the
• Occasionally pts present with ataxia of gait without motor and sensory involvement due to
involvement of the spinocerebellar tract.
• Pain induced by SLRT, neck flexion, or vertebral percussion may help to determine the
level of cord compression.
• Loss of sensation to pinprick is as common as loss of sensibility to vibration or position.
• The upper limit of the zone of sensory loss is often one or two vertebrae below the
site of compression.
• Motor examination
• Spastic weakness, spasticity
• Extensor plantar reflex and brisk DTR.
• Motor and sensory loss usually precedes autonomic dysfunction.
• Autonomic dysfunction
• Present with decreased anal tonus, decreased perineal sensation, and distended bladder.
• The absence of the anal wink reflex or the bulbocavernosus reflex confirms cord involvement.
• Residual volume of >150 mL suggests bladder dysfunction.
• Cauda equina syndrome: characterized by
• Low back pain
• Diminished sensation over the buttocks, posterior-superior thighs, and perineal area in a saddle
• Bowel and bladder dysfunction; impotence
• Absent bulbo-cavernous and DTR.
• Variable amount of lower-extremity weakness.
• The majority of cauda equine tumors are primary tumors of glial or nerve sheath origin; metastases are
• Full-length image of the cord by Contrast MRI
• Myelography : Reserved for pts who have poor MRIs or who cannot undergo MRI promptly.
• CT Erosion of the pedicles (the “winking owl” sign) is the earliest radiologic finding.
• Other radiographic changes include
• Increased intra-pedicular distance,
• Vertebral destruction,
• Lytic or sclerotic lesions,
• Scalloped vertebral bodies, and
• Vertebral body collapse.
• Goal of therapy
• Relief of pain
• Restoration/preservation of neurologic function
• Radiation therapy plus glucocorticoids is generally the initial t/t of choice.
• Up to 75% of pts treated when still ambulatory remain ambulatory, but only 10% of patients with
paraplegia recover walking capacity.
• INDICATIONS FOR SURGICAL INTERVENTION
• Unknown etiology,
• Failure of radiation therapy,
• Radioresistant tumor type (e.g., melanoma or renal cell cancer),
• Pathologic fracture dislocation, and
• Rapidly evolving neurologic symptoms
• TYPES OF SURGERY
• Posteriorly localized epidural deposits in the absence of vertebral body disease.
• Resection of the anterior vertebral body along with the tumor, followed by spinal stabilization
• Anterior or anterolateral epidural abscess.
• A RCT showed that pts who underwent surgery followed by radiotherapy (within 14 days)
retained the ability to walk significantly longer than those treated with radiotherapy alone.
• Chemotherapy may have a role in pts with chemosensitive tumors who have had prior
radiotherapy to the same region and who are not candidates for surgery.
• Patients with metastatic vertebral tumors may benefit from percutaneous vertebroplasty or
kyphoplasty, the injection of acrylic cement into a collapsed vertebra to stabilize the fracture.
• Pain palliation is common.
• Cement leakage seen in 10% of pts.
• Seen with initial infusion of human or humanized antibodies (e.g., rituximab,
gemtuzumab, trastuzumab, alemtuzumab, panitumumab, brentuximab vedotin)
• A/w fever, chills, nausea, asthenia, and headache in up to half of treated pts.
• Bronchospasm and hypotension occur in 1% of pts.
• Severe manifestations including pulmonary infiltrates, ARDS , and cardiogenic shock
• Lab manifestations include elevated hepatic aminotransferase levels, thrombocytopenia, and
prolongation of PT.
• Activation of immune effector processes (cells and complement) release of inflammatory
cytokines, s/a TNF-α, INF-gamma, IL-6, and IL-10 (Cytokine Release Syndrome[CRS]).
• Diphenhydramine, hydrocortisone, and acetaminophen can often prevent or suppress the
• If they occur, the infusion is stopped and restarted at half the initial infusion rate after the
symptoms have abated.
• Severe CRS may require intensive support for ARDS and resistant hypotension.
• Neutropenic enterocolitis (Typhlitis) is the inflammation and necrosis of the cecum and
surrounding tissues that may complicate the treatment of acute leukemia.
• Nevertheless, it may involve any segment of the GIT including small intestine, appendix, and
• Clinical presentation
• Right lower quadrant abdominal pain, often with rebound tenderness and a tense, distended
abdomen, in a setting of fever and neutropenia.
• Watery diarrhea (often containing sloughed mucosa)along with bleed.
• CT SCAN
• Marked bowel wall thickening, particularly in the cecum,
• Bowel wall edema,
• Mesenteric stranding, and
• Patients with bowel wall thickness >10 mm on USG have higher mortality rates.
• Pneumatosis intestinalis is a more specific finding, seen only in those with neutropenic
enterocolitis and ischemia.
• The combined involvement of the small and large bowel suggests a diagnosis of neutropenic
• Rapid institution of broad-spectrum antibiotics, bowel rest, and nasogastric suction.
• Surgical intervention
Reserved for severe cases of neutropenic enterocolitis with
Evidence of perforation,
Gangrenous bowel, or
GI bleed despite correction of any coagulopathy