Hematology/Oncology
9.1 Acute Leukemia
Cause: Lymphocytic and non-lymphocytic varieties. This will focus on acute lymphocytic (blastic) leukemia, or ALL. Two types of ALL, child and adult. Adult type is probably genetic, HLAlinked, autosomal recessive.
Epidem: Adult type represents 15% of adult leukemias. Incidence of childhood type is 32 million per yr. No increased incidence near power lines. Possible hydrocarbon exposure in parents as risk (Cancer Epidem Biomarkers Prev 1999;8:783).
78% are B cells; 17% are T-cell types; 5% have no markers using monoclonal antibodies; some also have myeloid antigens that correlate with worse prognosis. Prognostic factors for children not the same for T-cell and B-cell ALL (Leukemia 1999;13:1696).
Associated with chromosome #9 deletion that has interferon α and interferon β genes.
Also associated with translocation of chromosome #11 in adult (Blood 1999;94:2072).
Sx: Malaise, fever.
Si: Pallor, white plaque on lateral tongue (oral hairy leukoplakia) (Oral Dis 1999;5:76), hepatosplenomegaly, ecchymoses,
petechiae; rarely leukemia cutis, which resembles a viral exanthem type eruption (J Dermatol 1999;26:216).
petechiae; rarely leukemia cutis, which resembles a viral exanthem type eruption (J Dermatol 1999;26:216).
Crs: In children, now much higher cure rates, 70% 5-yr survivals. In adults, prognosis is much worse than in children; T-cell types have worst prognosis, rest susceptible to treatment; 20-30% cure currently.
Cmplc: Varicella zoster disease with 7% mortality; 6% recurrence in testes, prevent with irradiation, which decreases testosterone later; Pneumocystis carinii; CMV; progressive multifocal leukoencephalopathy; AML after chemotherapy in 4%; second primaries in 0.5% of children; sterility; opportunistic infection.
Lab: CBC with diff; metabolic profile including renal function, liver function, calcium, magnesium, phosphorus; UA and urine culture, CXR, and consider LP if looking for secondary infectious focus—consider PCR for specific infections (Ped Infect Dis J 1999;18:395).
Emergency Management:
Treat secondary infections.
Order/transfuse appropriate blood products as necessary.
Consult pt’s primary physician or arrange hematology/oncology consult (Med Ped Oncol 1999;32:1; J Clin Oncol 2000;18:547).
9.2 Primary CNS and Spinal Cord Neoplasms
Cause: Meningioma, lymphoma (Leuk Lymphoma 1995;19:223), medulloblastoma, gliomas, ependymoma, craniopharyngioma.
Epidem: Recent trends stable except for those > 85 yr of age (J Natl Cancer Inst 1999;91:1382). Environmental risk factors not wellproven (Cancer Epidem Biomarkers Prev 1994;3:197) which includes cell phone use (Nejm 2001;344:79). An increase in
CNS lymphoma in those with AIDS has occurred (J Natl Cancer Inst 1996;88:675).
CNS lymphoma in those with AIDS has occurred (J Natl Cancer Inst 1996;88:675).
Adults: 50% gliomas, 25% meningiomas.
Pediatrics: 50% gliomas; 25% medulloblastoma; 10% ependymoma; 5% craniopharyngioma.
Pathophys: Gliomas incorporate 4 subtypes: (1) Grade 1 is the astrocytoma; (2) Grade 2 is the glioma; (3) Grade 3 is the astroblastoma, aka anaplastic astrocytoma; and (4) Grade 4 is the glioblastoma. Glioma class of tumors most commonly in cerebellum and pons in peds; and spinal cord, cerebrum, and cerebellum in adults.
Sx: Medulloblastoma may present with cerebellar signs, such as ataxia; all may present with seizures; less likely headache, but possible including other signs of increased intracranial pressure.
Spinal cord symptoms may be confined to one nerve root or include “saddle” anesthesia and/or incontinence of bladder or bowel.
Si: Depends on location; craniopharyngiomas may present with bitemporal hemianopsia, obesity, diabetes insipidus, growth failure in children.
Spinal cord findings may include anesthesia, pain, and loss of patella or Achilles reflexes; consider Cauda Equina syndrome, if anesthetic in distribution of where one would sit in a saddle, overflow incontinence, lack of rectal tone, severe pain, and loss of Achilles and patellar reflexes—usually gradual in onset and may be asymmetric findings.
Crs:
Meningiomas are benign, yet can be recurrent.
Medulloblastomas are highly malignant with 30-70% 5-yr remission, 92% 5-yr survival, and perhaps 50% cure.
Glioma class tumors depend on grade; higher the grade, the worse the prognosis.
Craniopharyngiomas are slow-growing and at least 15-yr survival with treatment.
Cmplc: Panhypopit with post-op patients with craniopharyngiomas.
Spinal cord tumors may present with isolated nerve root findings, but also as Cauda Equina (L1-S5) or Conus Medullaris (S2-5) problems.
Lab: Neuroimaging with CT usually followed by MRI, check electrolytes, cortisol level, and TSH in those with pituitary locations.
N.B. MRI is procedure of choice if considering Cauda Equina or Conus Medullaris process, and should be done emergently. Also procedure of choice for diffuse brainstem glioma diagnosis (Neurosurgery 1993;33:1026,1029).
Emergency Management:
Treat secondary symptoms of nausea and pain.
Consider glucocorticoids, such as dexamethasone 4 mg tid for mass effect.
Consider prophylactic anti-epileptic, such as phenytoin if brain neoplasm, with or without seizures.
Neurosurgical consult, with arrangements for radiation treatment if Cauda Equina or Conus Medullaris problem.
9.3 Disseminated Intravascular Coagulation (DIC)
Cause: Two requirements: (1) reticuloendothelial system blockade by pregnancy, endotoxin, radiation, steroids, colloid, and (2) clotting system activated by:
Thromboplastin releaser, eg, frozen tissue (hypothermia), placenta, tumors, trypsin, snake venom, open brain trauma, renal transplant rejection; or
Defibrination agent, eg, amniotic fluid; or
Platelet factor 3 (phospholipid) release, eg, platelet clot, hemolysis, fat embolism, immune reaction; or
Activation of factor XII, eg, by endotoxin.
Epidem: More common than TTP. Increased incidence in OB patients especially with septic Ab, abruptio, eclampsia, hydatidiform mole, amniotic fluid embolus, missed Ab, retained dead fetus, fatty liver of pregnancy; leukemia, cancer, and all cases of severe tissue damage; freshwater drownings; Gram-negative sepsis (Jpn J Surg 1977;7:82).
Pathophys: Fibrinogen is low due to consumption and rapid lysis; tissue damage especially in CNS, lung, and kidneys from thrombotic ischemia.
Si: Palpable purpuric rash; hypotension; oozing/bleeding at all sites; shock.
Crs: Worse prognosis with extent of PT, PTT, platelet count, and/or thrombin time abnormalities (Thromb Haemost 1978;39:122); usually an acute and fulminant course, rarely chronic.
Cmplc: Renal cortical necrosis, ATN, Sheehan’s syndrome, acute cor pulmonale, adrenal insufficiency.
Diff Dx: Vasculitis; implicated infections include “benign” viruses such as varicella (Infection 1998;26:306); cold-induced coagulopathy.
Lab: CBC with diff (microangiopathic anemia with helmet cells and other fragments); metabolic profile including liver and renal markers; ESR = 0 secondary to afibrinogenemia; PT/PTT (PT very sensitive); D-dimer and FDP markedly elevated; fibrinogen < 40 mg% (Am J Hematol 1998;59:65); elevated AT III; UA. Low levels of factors II, VIII, and V (< 50% is diagnostic). Soluble fibrin as a pre-DIC marker (Acta Anaesthesiol Scand 1993;37:125).
Emergency Management:
Treat underlying cause.
Replace factors—consider FFP and platelets.
Perhaps heparinize to break consumptive cycle, LMWH has proponents vs unfractionated heparin (Thromb Res 1993;72:475; 1990;59:37); never do so in the face of liver disease, and only as a last resort if chronic cause and uncontrollable bleeding. Not advocated as a preventative therapy (J Emerg Med 1988;6:277).
Potential use of dermatan sulfate (Thromb Res 1994;74:65).
9.4 Febrile Neutropenia
Cause: Agranulocytosis (absolute neutrophil count < 500/mm3) due to:
Allergic directly as with chloramphenicol or via lupus, eg, from procainamide.
Autoimmune antibodies and occasionally, perhaps, killer T cells; idiopathic usually; ibuprofen-induced is reversible.
Direct drug toxic effect from chemotherapy, chloramphenicol.
Epidem: Type of opportunistic pathogen changing from Gram-neg to Gram-pos organism (Clin Infect Dis 1999;29:495); autoimmune type associated with rheumatoid Felty’s syndrome.
Allergic type: Delayed hypersensitivity T cells kill in marrow; drugs can act as hapten to induce.
Autoimmune type: Antibodies esp. to HLA surface antigens.
Sx: Fever, rigors, malaise, sore throat, cough.
Si: T > 38.3°C or 101°F (no rectal temperature), pharyngitis, rash, pulmonary findings or other clinical findings of infection (or recurrent infection).
Crs: Idiopathic autoimmune type very benign—rarely progresses to sepsis.
Cmplc: Sepsis.
Diff Dx: Drug fever; pulmonary embolus; genetic cyclic neutropenia.
Lab: CBC with diff; metabolic profile including liver markers; blood cultures × 2 with one from central line if present; UA and urine culture; CXR—those with lower respiratory tract infection fare worse (Infection 1998;26:349); PT/PTT if sepsis suspected; consider LP; cultures of any and all wounds.
Emergency Management:
Isolation.
Iv access.
Treat fever, caution with acetaminophen or with NSAIDs, if liver dysfunction.
Antibiotic: Imipenem-cilastin 500 mg iv q 6 hr, cefepime 1-2 gm iv q 12 hr, or meropenem 0.5-1 gm q 8 hr alone; or with aminoglycoside [peds (Ped Hematol Oncol 2000;17:93)], eg, gentamicin; combination therapy of qd ceftriaxone 80 mg/kg to 4 gm max or levofloxacin 750 mg iv, if β-Lactam allergy with gentamicin at 5 mg/kg unless creatinine clearance < 20 mL/min (see p236) in which case load at 2 mg/kg (Arch Dis Child 1999;80:125); or aztreonam 1-2 gm iv q 6-8 hr + vancomycin 15 mg/kg iv q 12 hr or 30 mg/kg iv qd; low-risk patients may have oral ciprofloxacin 500 mg bid and amoxicillin-clavulanate 875 mg bid (Nejm 1999;341:305). Use of ceftazidime has become reduced with elucidation of different lactamases.Related posts:
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