(01992 Harwood
Leukemia and Lymphoma, Vol. 8, pp. 3 15-31 8 Reprints available directly from the publisher Photocopying permitted by license only
Academic Publishers G m b H Printed in the United Kingdom
Leuk Lymphoma Downloaded from informahealthcare.com by Universitaets- und Landesbibliothek Duesseldorf on 01/20/14 For personal use only.
Acute Tumor Lvsis Svndrome in Hematologic Malignancies D. R. FLEMING and M. A. DOUKAS University of Kentucky, Division of Hematology/Oncology, Markey Cancer Center, Lexington, Kentucky, USA (Received 5 Ma)) 1992)
Acute tumor lysis syndrome (ATLS) represents one of the most urgent of all oncologic treatment related complications. This is due not only to its broad impact on organ dysfunction, but also to its relative ease of prevention and treatment when aware of its potential threat. Despite anecdotal experiences of ATLS in settings outside the use of chemotherapy, the majority of patients susceptible to ATLS can be predicted using clinical as well as laboratory parameters and prophylaxis can prevent this potentially lethal consequence of otherwise successful cancer therapeutics. This review article will attempt to bring the critical aspects involving ATLS together in order to delineate the pathophysiology as well as treatment of this generally avoidable entity. K E Y WORDS:
Acute leukemia agressive lymphoma allopurinol dialysis
hypercalcemia
hyperkalemia
whelming the hepatic and renal capabilities to metabolize and excrete lactic acid, acidemia develops. Evidence of rapid tumor cell destruction and potential Escalating hyperkalemia and concurrent hypocalceclinical consequences existed prior to the discovery of mia can result in various cardiac dysrhythmias, ending effective treatment of some of today’s most responsive in cardiac arrest4.’. A less acute problem is that of hematologic malignancies. Virchow first noted in 1859 renal failure, usually secondary to manifestations of an increased biproduct of rapid cell turnover reflected uric acid nephropathy with some possible influence of in the form of hyperuricemia in acute lymphocytic iatrongenic complications related to over alkalinleukemia patients. With the development of effective ization in the setting of phosphate-calcium distherapeutics over the last 25 years, it’s obvious that equilibrium6-’. rapid malignant cell destruction, through the use of ATLS has typically been detected in the setting of various treatment modalities, can result in potentially tumors reflecting high growth fractions, approaching lethal metabolic derangements. ATLS may be 100% in some instances. Also, tumor bulk and clinically silent, diagnosed only by laboratory effective therapy, usually in the form of chemotherapy, parameters reflecting relative hyperuricemia, hyper- have played a major role in determining who kalemia, hyperphosphatemia, and hypermagnesemia experiences ATLS8. While Burkitt’s lymphoma and secondary to the rapid release of intracellular acute leukemia patients constitute the majority of products’-2. Hypocalcemia can result as a con- patients experiencing ATLS, more treatment expersequence of the hyperpho~phatemia~.By over- ience and efficacy has led to more indolent hematologic disorders such as chronic lymphocytic leukemia manifesting ATLS9. Anecdotal experiences exist of ATLS involving various solid malignancies Address for correspondence: Donald R. Fleming, M.D., University of Kentucky, Division of Hematology/Oncology, 800 such as germ cell tumors, small cell lung carcinoma and medulloblastoma with extensive tumor Rose Street, Lexington, K Y 40536 0084, U.S.A.
BACKGROUND/PATHOPHYSIOLOGY
315
D. R. FLEMING AND M. A. DOUKAS
316
mass” Factors unrelated to the primary malignancy, such as the form of therapy, also influence the development of ATLS. While most often seen in the setting of chemotherapy administration, other treatments such as ionizing radiation, biologic response modifiers, hormonal therapy and glucocorticosteroids have resulted in ATLSI3 15. The syndrome has even been seen in cases of highly refractory malignancies treated with bone marrow transplantation. These situations were unique not only in that the patients had previously been extensively treated but also because they experienced the syndrome after the initial radiation portion of the tumor and marrow ablative prepatory therapy“. Certain factors endogenous to the patient are also felt to have an impact on the development and/or seriousness of ATLS. These factors include underlying renal insufficiency and an establishment catabolic state of the p’atient. An increasing catabolic state increases the reutilization of tumor lysis biproducts. However, with decreasing renal function the ability to dispose of these products is impaired . Each situation results in opposite influences on the severity of the ATLS”. Not only has the influence upon severity of ATLS been examined relating to the tumor histopathology, growth rate, tumor mass and therapeutics but also the influence of immunophenotyping. The predictability of ATLS on exposure to ionizing radiation has resulted in knowledge that malignancies involving B cell and activated T cells, as confirmed by flow cytometric techniques, are more likely to result in rapid tumor lysis. While these studies were based on murine cell models and ionizing radiation, evidence in human malignancies has supported these findings 6 , 1’.
Leuk Lymphoma Downloaded from informahealthcare.com by Universitaets- und Landesbibliothek Duesseldorf on 01/20/14 For personal use only.
”,
DIAGNOSIS/RISK FACTORS
In order for effective prophylactic management of ATLS to take place, diagnosis of such an entity should come about by laboratory means during the early asymptomatic period. This, as previously indicated, is accomplished by prudent monitoring prior to and at the initiation of therapy for high risk patients”. Occasionally in the exceptional situation, such as a chronic leukemia, solid malignancy patient, or the usage of non-conventional therapies such as biologic modifying agents or steroids, one can first become suddenly aware of ATLS through clinical developments. The symptoms are most often nausea, vomiting, lethargy, clouding of urine, renal colic and
even joint discomfort secondary to rapidly increasing uric acid levels2. Due to rapid tissue uptake and reutilization of potassium, serious cardiac dysrhythmias can be avoided. The rapid uptake is felt to be secondary to a conversion from a relatively potassium depleted state under rapid tumor growth 19. Essential in this setting is a non-acidemic state which allows intracellular uptake of potassium stores. The avoidance of acidemia also increases solubility of uric acid’ I . In avoiding acidemia, excessive alkalinization also must be avoided due to potential problems of calciuni deposition in the concomitant setting of hyperphosphatemia, leading to further problems with renal function and clinical hypocalcemia’.
PREVENTION/TREATMENT (see figure 1) Prior to discussing the proper management in patients with ATLS it is essential to try and prevent such episodes with the use of liberal volume administration and subsequent increased urine flow of greater than 100 cc/hr. Often 3 liters/m2/day with or without loop diuretics are recommended. The use of osmotic diuretics which have some supporters, are yet to be shown clinically superior23. Methods of reducing tumor mass by either pheresis (for leukemia) or surgical debulking is still controversial pending administration of the aforementioned steps”. Also, essential in the management as well as prevention of ATLS is the use of allopurinol, the popular and extensively utilized xanthine oxidane inhibitor to reduce completed conversion of nucleic acid biproducts to uric acid. In using allopurinol one must still be aware of possible side effects such as the occurrences of rashes, interstitial nephritis, fever and eosinophilia. Generally a starting dose of 100-300 mg/m2/day is recommended for prophylactic doses of allop~rinol~~. If despite aforementioned precautions or if an unpredictable case of ATLS develops, the management continues to involve monitoring urine output, serum chemistries and weight kinetics versus other methods to determine hemodynamic status. The management would include withholding further antitumor therapy until more effective diuresis results in significant decrease of tumor lysis biproducts as well as constitutional symptoms23.Also, management of acidemia can be achieved by administering an IV bicarbonate infusion as a source of sodium and continuing administration until the serum pH is greater than 7.0 but for reasons previously mentioned
ACUTE TUMOR LYSlS
317
RULE O U T PRE-TREATMENT ATLS AND WITHHOLD TREATMENT UNTIL ALL PARAMETERS CORRECTED
DETERMINED RISK (TUMOR MASS, HISTOPATHOLOGY, RENAL FUNCTION) I
I
I
I
Assessed us Increased Risk Putient 1. Monitor electrolytes q. 4"-6',
Leuk Lymphoma Downloaded from informahealthcare.com by Universitaets- und Landesbibliothek Duesseldorf on 01/20/14 For personal use only.
2. 3. 4. 5.
LOW Risk Putient 1. Observe for clinical symptoms 2. Routine electrolytes as indicated
Allopurinol 100-300 mg/m*/day Increase urine output to 3 liters/m2/day Diuretics (loop or osmotic) if necessary ? transfer to acute care unit
/
D x of Acute Tumor Qsis Syndrome I . Transfer to acute care setting and monitor hemodynamic parameters
2. Increase hydration using diuretics as necessary 3. Increase allopurinol up to 500 mg/m2/day 4. Na bicarb as sodium source to keep urine pH between 7.1-7.5, (utilize acetazolomide if volume load a problem) 5. Replace calcium 6. Maintain control of potassium acutely with insulin glucose and/or Na bicarb and chronically with exchange resins 7. Control phosphate oral utilizing binders 8. If metabolic derangements persist, renal function deteriorate and/or problem with volume status, begin dialysis procedures Figure 1
no more alkaline than a pH of 7.5. When volume status becomes a management problem itself due to underlying cardiac dysfunction and/or renal insufficiency the use of the acetylcholinesterase inhibitor, acetazolamide at a dose of 250-500 mg IV/day x 2 days to induce urinary alkalinization and subsequent prevention of uric acid nephropathology can be utilized. Should hyperkalemia become a problem, acute and temporary management can be accomplished by insulin in conjunction with the bicarbonate administration along with chronic measures such as the use of potassium exchange resins orally3. Hyperphosphatemia while not a tremendous threat can be dealt with initially by using aluminum containing phosphate binders along with diuresis. During these attempts at correcting the metabolic derangements plaguing the patient diagnosed with ATLS, monitoring serum chemistries every three to four hours along with frequent EKGs are recommended in order to keep abreast of a patient's potentially rapidly changing status. Often management is best handled in an acute care setting such as an intensive care unit, where aggressive hemodynamic monitoring can take place. The ultimate means of handling ATLS should
previously mentioned methods fail, is the use of either peritoneal or hemodialysis. Each method has its own advocates. Newer methods such as hemofiltration techniques may also be useful. Indications for such interventions are decreasing urine output despite attempts at diuresis, increasing serum creatinine, potassium, uric acid, volume status or decreasing calcium levels24 26. In addition to problems related to massive tumor lysis, patients experiencing ATLS are subject to other sites of organ failure, such as pulmonary decompensation secondary to difficulties handling the aggressive volume administration in a patient with borderline cardiovascular function. Another dilemma is to determine which organ systems are failing secondary to ATLS and those doing so as a consequence of concomitant primary processes. These patients are often in a high risk group due to factors such as infectious disease, disseminated intravascular coagulation (DIC), and direct toxicity of the various therapeutic technique^^.^'. While ATLS for the most part can be predicted as a potential risk in the setting of histopathologic diagnosis of acute leukemias and aggressive lymphomas the increasing use of dose intensive approaches may result in more common
D. R. FLEMING AND M. A. DOUKAS
318
Leuk Lymphoma Downloaded from informahealthcare.com by Universitaets- und Landesbibliothek Duesseldorf on 01/20/14 For personal use only.
place situations with ATLS as a potential risk during initiation of such treatment. Only through meticulous chemical and clinical observation can serious manifestations of ATLS such as acute cardiac arrest and renal failure be prevented. Also, candidates for ATLS are also candidates for other serious mechanisms of multiple organ failure such as those related to infection, anti-tumor therapy and the primary malignancy itself.
REFERENCES I . Pouchedly, C. (1973). Hyperuricemia in leukemia and lymphoma Part I, New York State Journul of Medicine; May, 1085-92. 2. Groeger, J. S. (1991). Critical Care of the Cancer Patient; 2nd edn, pp 155-58 St. Louis Mosby Year Book Inc. 3. Sondheimer, J. H. and Migdal, S. D. (1987). Toxic nephropathies. Critical Care Clinics, 3(4), 883-907. 4. Thomas, C. R., Jr. and Oodhia, N. (1991). Common emergencies in cancer medicine: metabolic syndromes, Journal of’ National Medical Associution, 83(9), 809- 18. 5. Stokes, D. N. (1990). Tumor lysis syndrome and the anaesthesiologist: Intensive care aspects of paediatric oncology, Seminars In Surgicul Oncology, 6(3), 1 5 6 6 I. 6. Eltinger, D. S., Harker, W. G., Gerry, H. W., et a/. (1978). Hyperphosphatemia, hypocalcemia and transient renal failure; Journul of American Medical Associution, 239, 2472-74. 7. O’Conner, L. R., Klein, K. L. and Bethune, J. E. (1977). Hyperphosphatemia in lactic acidosis, Neb' England Journol uf’ Medicine, 291, 707-9. 8. Editorial (1981): Tumor lysis syndrome; Lancet, 849. 9. McCroskey. R. D., Mosher, D. F., Spencer, C. D., Prendergrast, E. and Longo, W. L. (1990). Acute tumor lysis syndrome and treatment response in patients treated for refractory chronic lymphocytic leukemia with short-course, high dose cytosine arabinoside, cisplatinum and etoposide, Cuncer, 66, 246-50. 10. Barton, J. C. (1989). Tumor lysis syndrome in nonhematopoeitic neoplasms. Cuncer, 64, 738-40. 11. Hussein, A. M. and Feun, L. G . (1990). Tumor lysis syndrome after induction chemotherapy in small-cell lung carcinoma, American Journal of Clinical Oncology, 13(1), 10-1 3.
12. Tomlinson, G . C. and Solberg, L. A. (1984). Acute tumor lysis syndrome with metastatic medulloblastoma. Cancer, 53, 1783- 5. 13. Sparano, J., Ramirez, M. and Wiernick. P. H. (1990). Increasing recognition of corticosteroid induced tumor lysis syndrome in non-Hodgkins lymphoma, Cancer, 65, 1072-75. 14. Cech, P., Block, J. B., Cone, L. A. and Tome, R. (1986). Tumor lysis syndrome after tamoxifen flare, New Engnglund Journul of’ Medicine. 315, 263-64. 15. Fer, M. F.. Bottin, D. B. and Sherwin, S. A. (1984). Atypical tumor lysis syndrome in a patient with T-cell lymphoma treated with recombinant leukocyte interferon, Americ,un Journul of’ Medic,ine, 11,953-56. 16. Fleming, D. R., Henslee-Downey, J. and Coffey, C. (1991). Radiation induced tumor lysis syndrome in the bone marrow transplantation setting, Bone Marrow Transplantation, 8,235-6. 17. Schilsky. R . L. (1984). Renal and metabolic toxicities of cancer treatment in toxicity of chemotherapy (M. C. Perry and J . W. Yarboro, eds.) Grune and Stratton, Orlando, Fla, 317-42. 18. Anderson, R. E. and Williams, W. L. (1987). Radiosensitivity of T & B lymphocytes, Americun Journul ~f’P(ithoIog.v, 89, 367-78. 19. Tsokos, G. C., Balow, J. E., Spiegel, R. J., et al. (1981). Renal and metabolic complications of undifferentiated and lymphoblastic lymphomas. Mediic,inr, 60, 21 8-29. 20. Frei, E., 111, Bentzel, C., Riesgelbach, R. and Block, J. (1963). Renal complications of neoplastic disease, Journal of Chronic, Disease, 16, 757. 21. Band, P. R., Silverberg, D. S. and Henderson, J. F. (1970). Xanthine nephropathy in patients treated with allopurinol; New England Journal of Medicine, 382, 354-57. 22. Williams. A. W. and Wilson, D. M. (1990).Uric acid metabolism in humans, Swninars in NiJphrolo
Leukemia and Lymphoma, Vol. 8, pp. 3 15-31 8 Reprints available directly from the publisher Photocopying permitted by license only
Academic Publishers G m b H Printed in the United Kingdom
Leuk Lymphoma Downloaded from informahealthcare.com by Universitaets- und Landesbibliothek Duesseldorf on 01/20/14 For personal use only.
Acute Tumor Lvsis Svndrome in Hematologic Malignancies D. R. FLEMING and M. A. DOUKAS University of Kentucky, Division of Hematology/Oncology, Markey Cancer Center, Lexington, Kentucky, USA (Received 5 Ma)) 1992)
Acute tumor lysis syndrome (ATLS) represents one of the most urgent of all oncologic treatment related complications. This is due not only to its broad impact on organ dysfunction, but also to its relative ease of prevention and treatment when aware of its potential threat. Despite anecdotal experiences of ATLS in settings outside the use of chemotherapy, the majority of patients susceptible to ATLS can be predicted using clinical as well as laboratory parameters and prophylaxis can prevent this potentially lethal consequence of otherwise successful cancer therapeutics. This review article will attempt to bring the critical aspects involving ATLS together in order to delineate the pathophysiology as well as treatment of this generally avoidable entity. K E Y WORDS:
Acute leukemia agressive lymphoma allopurinol dialysis
hypercalcemia
hyperkalemia
whelming the hepatic and renal capabilities to metabolize and excrete lactic acid, acidemia develops. Evidence of rapid tumor cell destruction and potential Escalating hyperkalemia and concurrent hypocalceclinical consequences existed prior to the discovery of mia can result in various cardiac dysrhythmias, ending effective treatment of some of today’s most responsive in cardiac arrest4.’. A less acute problem is that of hematologic malignancies. Virchow first noted in 1859 renal failure, usually secondary to manifestations of an increased biproduct of rapid cell turnover reflected uric acid nephropathy with some possible influence of in the form of hyperuricemia in acute lymphocytic iatrongenic complications related to over alkalinleukemia patients. With the development of effective ization in the setting of phosphate-calcium distherapeutics over the last 25 years, it’s obvious that equilibrium6-’. rapid malignant cell destruction, through the use of ATLS has typically been detected in the setting of various treatment modalities, can result in potentially tumors reflecting high growth fractions, approaching lethal metabolic derangements. ATLS may be 100% in some instances. Also, tumor bulk and clinically silent, diagnosed only by laboratory effective therapy, usually in the form of chemotherapy, parameters reflecting relative hyperuricemia, hyper- have played a major role in determining who kalemia, hyperphosphatemia, and hypermagnesemia experiences ATLS8. While Burkitt’s lymphoma and secondary to the rapid release of intracellular acute leukemia patients constitute the majority of products’-2. Hypocalcemia can result as a con- patients experiencing ATLS, more treatment expersequence of the hyperpho~phatemia~.By over- ience and efficacy has led to more indolent hematologic disorders such as chronic lymphocytic leukemia manifesting ATLS9. Anecdotal experiences exist of ATLS involving various solid malignancies Address for correspondence: Donald R. Fleming, M.D., University of Kentucky, Division of Hematology/Oncology, 800 such as germ cell tumors, small cell lung carcinoma and medulloblastoma with extensive tumor Rose Street, Lexington, K Y 40536 0084, U.S.A.
BACKGROUND/PATHOPHYSIOLOGY
315
D. R. FLEMING AND M. A. DOUKAS
316
mass” Factors unrelated to the primary malignancy, such as the form of therapy, also influence the development of ATLS. While most often seen in the setting of chemotherapy administration, other treatments such as ionizing radiation, biologic response modifiers, hormonal therapy and glucocorticosteroids have resulted in ATLSI3 15. The syndrome has even been seen in cases of highly refractory malignancies treated with bone marrow transplantation. These situations were unique not only in that the patients had previously been extensively treated but also because they experienced the syndrome after the initial radiation portion of the tumor and marrow ablative prepatory therapy“. Certain factors endogenous to the patient are also felt to have an impact on the development and/or seriousness of ATLS. These factors include underlying renal insufficiency and an establishment catabolic state of the p’atient. An increasing catabolic state increases the reutilization of tumor lysis biproducts. However, with decreasing renal function the ability to dispose of these products is impaired . Each situation results in opposite influences on the severity of the ATLS”. Not only has the influence upon severity of ATLS been examined relating to the tumor histopathology, growth rate, tumor mass and therapeutics but also the influence of immunophenotyping. The predictability of ATLS on exposure to ionizing radiation has resulted in knowledge that malignancies involving B cell and activated T cells, as confirmed by flow cytometric techniques, are more likely to result in rapid tumor lysis. While these studies were based on murine cell models and ionizing radiation, evidence in human malignancies has supported these findings 6 , 1’.
Leuk Lymphoma Downloaded from informahealthcare.com by Universitaets- und Landesbibliothek Duesseldorf on 01/20/14 For personal use only.
”,
DIAGNOSIS/RISK FACTORS
In order for effective prophylactic management of ATLS to take place, diagnosis of such an entity should come about by laboratory means during the early asymptomatic period. This, as previously indicated, is accomplished by prudent monitoring prior to and at the initiation of therapy for high risk patients”. Occasionally in the exceptional situation, such as a chronic leukemia, solid malignancy patient, or the usage of non-conventional therapies such as biologic modifying agents or steroids, one can first become suddenly aware of ATLS through clinical developments. The symptoms are most often nausea, vomiting, lethargy, clouding of urine, renal colic and
even joint discomfort secondary to rapidly increasing uric acid levels2. Due to rapid tissue uptake and reutilization of potassium, serious cardiac dysrhythmias can be avoided. The rapid uptake is felt to be secondary to a conversion from a relatively potassium depleted state under rapid tumor growth 19. Essential in this setting is a non-acidemic state which allows intracellular uptake of potassium stores. The avoidance of acidemia also increases solubility of uric acid’ I . In avoiding acidemia, excessive alkalinization also must be avoided due to potential problems of calciuni deposition in the concomitant setting of hyperphosphatemia, leading to further problems with renal function and clinical hypocalcemia’.
PREVENTION/TREATMENT (see figure 1) Prior to discussing the proper management in patients with ATLS it is essential to try and prevent such episodes with the use of liberal volume administration and subsequent increased urine flow of greater than 100 cc/hr. Often 3 liters/m2/day with or without loop diuretics are recommended. The use of osmotic diuretics which have some supporters, are yet to be shown clinically superior23. Methods of reducing tumor mass by either pheresis (for leukemia) or surgical debulking is still controversial pending administration of the aforementioned steps”. Also, essential in the management as well as prevention of ATLS is the use of allopurinol, the popular and extensively utilized xanthine oxidane inhibitor to reduce completed conversion of nucleic acid biproducts to uric acid. In using allopurinol one must still be aware of possible side effects such as the occurrences of rashes, interstitial nephritis, fever and eosinophilia. Generally a starting dose of 100-300 mg/m2/day is recommended for prophylactic doses of allop~rinol~~. If despite aforementioned precautions or if an unpredictable case of ATLS develops, the management continues to involve monitoring urine output, serum chemistries and weight kinetics versus other methods to determine hemodynamic status. The management would include withholding further antitumor therapy until more effective diuresis results in significant decrease of tumor lysis biproducts as well as constitutional symptoms23.Also, management of acidemia can be achieved by administering an IV bicarbonate infusion as a source of sodium and continuing administration until the serum pH is greater than 7.0 but for reasons previously mentioned
ACUTE TUMOR LYSlS
317
RULE O U T PRE-TREATMENT ATLS AND WITHHOLD TREATMENT UNTIL ALL PARAMETERS CORRECTED
DETERMINED RISK (TUMOR MASS, HISTOPATHOLOGY, RENAL FUNCTION) I
I
I
I
Assessed us Increased Risk Putient 1. Monitor electrolytes q. 4"-6',
Leuk Lymphoma Downloaded from informahealthcare.com by Universitaets- und Landesbibliothek Duesseldorf on 01/20/14 For personal use only.
2. 3. 4. 5.
LOW Risk Putient 1. Observe for clinical symptoms 2. Routine electrolytes as indicated
Allopurinol 100-300 mg/m*/day Increase urine output to 3 liters/m2/day Diuretics (loop or osmotic) if necessary ? transfer to acute care unit
/
D x of Acute Tumor Qsis Syndrome I . Transfer to acute care setting and monitor hemodynamic parameters
2. Increase hydration using diuretics as necessary 3. Increase allopurinol up to 500 mg/m2/day 4. Na bicarb as sodium source to keep urine pH between 7.1-7.5, (utilize acetazolomide if volume load a problem) 5. Replace calcium 6. Maintain control of potassium acutely with insulin glucose and/or Na bicarb and chronically with exchange resins 7. Control phosphate oral utilizing binders 8. If metabolic derangements persist, renal function deteriorate and/or problem with volume status, begin dialysis procedures Figure 1
no more alkaline than a pH of 7.5. When volume status becomes a management problem itself due to underlying cardiac dysfunction and/or renal insufficiency the use of the acetylcholinesterase inhibitor, acetazolamide at a dose of 250-500 mg IV/day x 2 days to induce urinary alkalinization and subsequent prevention of uric acid nephropathology can be utilized. Should hyperkalemia become a problem, acute and temporary management can be accomplished by insulin in conjunction with the bicarbonate administration along with chronic measures such as the use of potassium exchange resins orally3. Hyperphosphatemia while not a tremendous threat can be dealt with initially by using aluminum containing phosphate binders along with diuresis. During these attempts at correcting the metabolic derangements plaguing the patient diagnosed with ATLS, monitoring serum chemistries every three to four hours along with frequent EKGs are recommended in order to keep abreast of a patient's potentially rapidly changing status. Often management is best handled in an acute care setting such as an intensive care unit, where aggressive hemodynamic monitoring can take place. The ultimate means of handling ATLS should
previously mentioned methods fail, is the use of either peritoneal or hemodialysis. Each method has its own advocates. Newer methods such as hemofiltration techniques may also be useful. Indications for such interventions are decreasing urine output despite attempts at diuresis, increasing serum creatinine, potassium, uric acid, volume status or decreasing calcium levels24 26. In addition to problems related to massive tumor lysis, patients experiencing ATLS are subject to other sites of organ failure, such as pulmonary decompensation secondary to difficulties handling the aggressive volume administration in a patient with borderline cardiovascular function. Another dilemma is to determine which organ systems are failing secondary to ATLS and those doing so as a consequence of concomitant primary processes. These patients are often in a high risk group due to factors such as infectious disease, disseminated intravascular coagulation (DIC), and direct toxicity of the various therapeutic technique^^.^'. While ATLS for the most part can be predicted as a potential risk in the setting of histopathologic diagnosis of acute leukemias and aggressive lymphomas the increasing use of dose intensive approaches may result in more common
D. R. FLEMING AND M. A. DOUKAS
318
Leuk Lymphoma Downloaded from informahealthcare.com by Universitaets- und Landesbibliothek Duesseldorf on 01/20/14 For personal use only.
place situations with ATLS as a potential risk during initiation of such treatment. Only through meticulous chemical and clinical observation can serious manifestations of ATLS such as acute cardiac arrest and renal failure be prevented. Also, candidates for ATLS are also candidates for other serious mechanisms of multiple organ failure such as those related to infection, anti-tumor therapy and the primary malignancy itself.
REFERENCES I . Pouchedly, C. (1973). Hyperuricemia in leukemia and lymphoma Part I, New York State Journul of Medicine; May, 1085-92. 2. Groeger, J. S. (1991). Critical Care of the Cancer Patient; 2nd edn, pp 155-58 St. Louis Mosby Year Book Inc. 3. Sondheimer, J. H. and Migdal, S. D. (1987). Toxic nephropathies. Critical Care Clinics, 3(4), 883-907. 4. Thomas, C. R., Jr. and Oodhia, N. (1991). Common emergencies in cancer medicine: metabolic syndromes, Journal of’ National Medical Associution, 83(9), 809- 18. 5. Stokes, D. N. (1990). Tumor lysis syndrome and the anaesthesiologist: Intensive care aspects of paediatric oncology, Seminars In Surgicul Oncology, 6(3), 1 5 6 6 I. 6. Eltinger, D. S., Harker, W. G., Gerry, H. W., et a/. (1978). Hyperphosphatemia, hypocalcemia and transient renal failure; Journul of American Medical Associution, 239, 2472-74. 7. O’Conner, L. R., Klein, K. L. and Bethune, J. E. (1977). Hyperphosphatemia in lactic acidosis, Neb' England Journol uf’ Medicine, 291, 707-9. 8. Editorial (1981): Tumor lysis syndrome; Lancet, 849. 9. McCroskey. R. D., Mosher, D. F., Spencer, C. D., Prendergrast, E. and Longo, W. L. (1990). Acute tumor lysis syndrome and treatment response in patients treated for refractory chronic lymphocytic leukemia with short-course, high dose cytosine arabinoside, cisplatinum and etoposide, Cuncer, 66, 246-50. 10. Barton, J. C. (1989). Tumor lysis syndrome in nonhematopoeitic neoplasms. Cuncer, 64, 738-40. 11. Hussein, A. M. and Feun, L. G . (1990). Tumor lysis syndrome after induction chemotherapy in small-cell lung carcinoma, American Journal of Clinical Oncology, 13(1), 10-1 3.
12. Tomlinson, G . C. and Solberg, L. A. (1984). Acute tumor lysis syndrome with metastatic medulloblastoma. Cancer, 53, 1783- 5. 13. Sparano, J., Ramirez, M. and Wiernick. P. H. (1990). Increasing recognition of corticosteroid induced tumor lysis syndrome in non-Hodgkins lymphoma, Cancer, 65, 1072-75. 14. Cech, P., Block, J. B., Cone, L. A. and Tome, R. (1986). Tumor lysis syndrome after tamoxifen flare, New Engnglund Journul of’ Medicine. 315, 263-64. 15. Fer, M. F.. Bottin, D. B. and Sherwin, S. A. (1984). Atypical tumor lysis syndrome in a patient with T-cell lymphoma treated with recombinant leukocyte interferon, Americ,un Journul of’ Medic,ine, 11,953-56. 16. Fleming, D. R., Henslee-Downey, J. and Coffey, C. (1991). Radiation induced tumor lysis syndrome in the bone marrow transplantation setting, Bone Marrow Transplantation, 8,235-6. 17. Schilsky. R . L. (1984). Renal and metabolic toxicities of cancer treatment in toxicity of chemotherapy (M. C. Perry and J . W. Yarboro, eds.) Grune and Stratton, Orlando, Fla, 317-42. 18. Anderson, R. E. and Williams, W. L. (1987). Radiosensitivity of T & B lymphocytes, Americun Journul ~f’P(ithoIog.v, 89, 367-78. 19. Tsokos, G. C., Balow, J. E., Spiegel, R. J., et al. (1981). Renal and metabolic complications of undifferentiated and lymphoblastic lymphomas. Mediic,inr, 60, 21 8-29. 20. Frei, E., 111, Bentzel, C., Riesgelbach, R. and Block, J. (1963). Renal complications of neoplastic disease, Journal of Chronic, Disease, 16, 757. 21. Band, P. R., Silverberg, D. S. and Henderson, J. F. (1970). Xanthine nephropathy in patients treated with allopurinol; New England Journal of Medicine, 382, 354-57. 22. Williams. A. W. and Wilson, D. M. (1990).Uric acid metabolism in humans, Swninars in NiJphrolo
