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A long-term prospective clinical study of oral complications during conventional chemotherapy for acute leukemia
A long-term prospective clinical study of oral complications during conventional chemotherapy for acute leukemia Anthony P. Barrett, B.D.Sc., Ph.D.*, WESTMEAD
HOSPITAL
DENTAL
CLINICAL
Westmead, New South Wales, Australia SCHOOL
AND
DEPARTMENT
OF MEDICINE
Oral complications were detected during 89% of hospital admissions for treatment of acute leukemia in adults. Changes that reflected the underlying myelosuppression and general immunosuppression predominated. Hemorrhagic phenomena (77%), neutropenic ulceration (49%), and herpes simplex virus infections (39%) were the most common. (ORAL SURC. ORAL MED. ORAL PATHOL. 1987;63:313-6)
A
range of oral complications may occur during remission-induction therapy for acute leukemia. These may be classified according to whether they are a direct consequence of the leukemic process or of the chemotherapy used in its management, or whether they occur indirectly as a result of underlying myelosuppression and general immunosupression.l** This range of possible changes has been extended in allogeneic bone marrow transplantation to include oral manifestations of acute and chronic graft-versus-host disease.3-5 The aim of this prospective clinical study was to determine the range and incidence of oral complications that occurred in a group of patients who underwent intensive conventional chemotherapy for acute leukemia. MATERIALS AND METHODS
I examined forty-four adult patients with acute leukemia during 57 separate hospital admissions over a 42-month period. Patients were examined initially within 24 to 72 hours after their arrival at the hospital, before treatment commenced, and then were examined on a daily basis until they were discharged or died. All patients received intensive remission-induction chemotherapy for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). During a total of 47 admissions, those with AML (35 patients) received one or more courses of *Staff Specialist Clinical School.
(Oral
Diagnosis),
Westmead
Hospital
Dental
chemotherapy involving a three-drug combination of daunorubicin, cytosine arabinoside, and 6-thioguanine (DAT). Five of these patients also received acridinylanisidine (m-AMSA) after a poor response to DAT. Those with ALL (9 patients/ 10 admissions) were managed with combination therapy, including vincristine sulfate, prednisone, daunorubicin, cytosine arabinoside, asparaginase, 6-mercaptopurine, and methotrexate, supplemented with central nervous system radiotherapy. Clinical examination was supplemented (where applicable) with fungal, viral, and bacterial culture methods and exfoliative cytopathologic study.6-8 Patients were encouraged to maintain existing oral hygiene practices-or upgrade oral hygiene if necessary-and instructed to use a mouthwash of bicarbonate of soda in water followed by topical nystatin or amphotericin suspensions four times daily throughout their hospitalization.‘*6 Chemical antiplaque agents, such as chlorhexidine preparations, were not used in this study. RESULTS
The range and incidence of oral complications are shown in Table I; these are grouped according to a previously reported classification system.‘, * Oral changes were found during 89% of the admissions. Leukemic
infiltration
Three patients had overt signs of direct leukemic cell infiltration of oral tissues. Tonsillar infiltration, which resolved with effective chemotherapy, was 313
314
Barrett
Oral March.
Table I. Summary
Group* AML (N = 47) ALL (N = 10) Combined total (N = 57) *AML:
Acute
ttonsillar
myeloid
of oral complications
during 57 admissions for acute leukemia
Gingival or tonsillarf inJiltration
Drug-induced ulceration
2(4%) 1 (IO%)? 3 (5%)
2 (4%) 2 (20%) 4 (7%)
leukemia.
ALL:
Acute
lymphoblastic
Bruising and bleeding 41 (87%) 3 (30%) 44 (77%)
Herpes simplex infection
Neutropenic ulceration 26 (55%) 2 (20%) 28 (49%)
19 (40%) 3 (30%) 22 (39%)
Candidiasis 12 (26%) 5 (50%) 17 (30%)
1 ~$~%~f 8 (17%‘) I (10%) 9 (16%)
leukemia.
infiltration.
seen in one patient at initial presentation of ALL. In one patient AML (monocytic type) was diagnosed as such after the patient consulted a periodontist about gingival enlargement. This also resolved with effective chemotherapy. Profound gingival infiltration developed in another patient with AML (monoblastic type) in the terminal stages of his disease. Drug-induced
ulceration
Oral mucosal breakdown and ulceration as a direct consequence of drug toxicity were seen in only four patients. Ulceration was not seen in relation to DAT; however, extensive breakdown occurred in two of five patients who received m-AMSA after a poor response to- DAT. Two patients with ALL experienced methotrexate-induced ulceration; severe ulceration occurred in one after a single 15 mg intrathecal dose, and mild ulceration occurred in a second after a high-dose (750 mg) intravenous infusion. Predisposing factors were not apparent. Bruising
Surg. I987
and bleeding
Oral bruising and/or frank bleeding were observed during 77% of the admissions. This was more common during admissions for AML (41 of 47) than for ALL (3 of 10). Furthermore, only isolated petechiae and relatively minor ecchymoses were observed in patients with ALL. In contrast, multiple hemorrhagic bullae (25 of 41), frank bleeding from gingivae or mucosal lesions (10 of 41) and/or deep muscle and tissue plane hematomas (3 of 41) were also observed in patients with AML. The greater incidence and severity of oral bruising and bleeding in the AML group were a reflection of the greater overall degree and duration of thrombocytopenia seen in that group9 rather than a suggestion of impaired platelet function in AML (compared to ALL), as proposed by Stafford and colleaguesLo in one study. Neutropenic
ulceration
Neutropenic ulceration of the oral mucosa was common (49% of the admissions), and the incidence
was greater in the patients with AML (55%) than in those with ALL (20%). This appeared to be a reflection of the significantly greater degree and duration of neutropenia in the AML group. While all patients with AML experienced profound neutropenia (levels < lOO/mm’), only 50% of those with ALL did so. Furthermore, the duration of neutropenia (levels <1000/mm3) was longer in patients with AML (average: 48 days) than in those with ALL (average: 26 days). This was statistically significant (t test, p < 0.05). Herpes
simplex
virus infection
Orofacial mucocutaneous infection by herpes simplex virus was found in 22 of 57 (39%) admissions. Intraoral mucosal involvement occurred on 13 of 22 occasions. Acyclovir was administered to six patients by intravenous infusion (5 mg/kg body weight) at 8-hour intervals for 5 to 8 days; one patient promptly became afebrile, indicating that-in the absence of bone marrow recovery or changes to existing antibiotic therapy-the infection had disseminated. Candidiasis
Oropharyngeal candidiasis occurred in 17 (30%) patients. Poor patient compliance with topical antifungals and/or failure of nystatin to prevent colonization6 were implicated in all cases. In one patient with disseminated candidiasis at postmortem examination, systemic access from the oral cavity appeared likely through sites of colonized neutropenic ulceration. Bacterial
infections
Localized dental/periodontal infections occurred in seven patients. Despite repeated blood cultures, bacteria were not isolated from the peripheral circulation in any case. Five infections quickly resolved with intravenous benzylpenicillin, and the remaining two patients, who had gingival cellulitis,* responded to intravenous metronidazole. In another two patients, generally innocuous oral commensal bacteria (Leptotrichia buccalis in one case and Strepto-
Volume Number
63 3
Oral complications
coccus mitis in the second) were isolated on blood culture during febrile episodes. Systemic access appeared likely in both cases through sites of extensive oral neutropenic ulceration. Oral infections by opportunistic enteric pathogens-as described by Dreizen and colleagues”-were not seen. DISCUSSION
Friedreich12 (1857) is credited with the first detailed account of a patient who died of acute leukemia, with evidence of weakness, hemorrhagic tendency, hepatosplenomegaly, and oral ulceration. Since that time, oral mucosal complications in patients with leukemia-particularly acute leukemia-have become accepted as common features of the disease and its treatment. The results of the present study, in which one or more oral changes occurred in 89% of hospital admissions for acute leukemia, confirmed this. Leukemic infiltration of oral tissues was an uncommon finding in this study. This finding-that gingival infiltration occurred during only 2 of 57 (3.5%) admissions--corresponds with that of Dreizen and colleagues,‘3 who reported it in 38 of 1076 (3.6%) patients in their study. Furthermore, as observed by Dreizen13: (a) gingival infiltration was not confirmed to acute monocytic leukemia (of which it was originally considered pathognomonic’4) but occurred in the present study in a case of acute monoblastic leukemia and (2) local predisposing factors were not apparent. Drug-induced oral mucosal ulceration occurred during only four (7%) admissions and was unexpected in all four cases. As previously observed, predisposing factors were not identified.‘” I6 Considering the chemotherapeutic agents and administration, schedules used in this study are similar to those employed worldwide and, considering that the incidence of drug-induced ulceration was low (7%) compared to the overall incidence of oral changes (89%), clinicians should avoid dismissal of oral ulceration in these patients as simply drug-induced “mucositis” and should carefully consider other causes (e.g., neutropenic ulceration and herpes simplex infection) in the differential diagnosis of oral ulceration. More common than those oral mucosal changes that reflected the direct consequences of the leukemia and its management were those lesions that reflected the underlying myelosuppression and general immunosuppression. Hemorrhagic phenomena and neutropenic ulceration were the most common changes and occurred in 77% and 49% of admissions, respectively. In most earlier studies of oral changes in patients
during chemotherapy for acute leukemia
315
with acute leukemia, orofacial infection by herpes simplex virus has either not been reported or has been reported as uncommon-particularly oral mucosal involvement.“~ 17-19Recent studies including the present, however, indicate that these orofacial infections are indeed common in patients who received conventional chemotherapy for acute leukemia (39% admissions here) and may occur even more often in recipients of bone marrow transplantation (up to 60% of cases).4s7 This finding is probably primarily a result of an increasing awareness of the variability of clinical presentation of these infections in the immunosuppressed and increased use of specific diagnostic aids, such as exfoliative cytopatholoiitY*
I. 2. 1.8
Despite routine topical antifungal prophylaxis, clinical candidiasis occurred at some stage during 17 (30%) admissions. In the earlier phase of the study, this appeared to be principally a reflection on the limited ability of nystatin to eliminate and prevent candidal colonization of the oral cavity.6 In all cases where topical amphotericin B appeared ineffective, poor patient compliance was implicated, particularly in patients in the terminal stages of their disease. Apart from two patients with evidence of septicemia caused by oral commensals, oral bacterial infections in these patients appeared of minor local significance only. Aggressive orofacial mucocutaneous infections by enteric pathogens, of the type reported by Dreizen and colleagues,” were not found in any patient in this study. Where enteric pathogens were isolated from swabs of oral lesions (e.g., neutropenic ulceration), they appeared to be local contaminants only. They did not appear to alter the clinical characteristics of the various lesions in any way; nor were they seen to be related to septicemia in any case. In conclusion, oral complications are common (and frequently multiple) in patients who receive aggressive remission-induction chemotherapy for acute leukemia. Differentiation of the various oral changes in these patients through daily observations promotes early intervention of complications, such as herpes simplex virus and candidal infections, and provides the clinician with an ongoing indicator of systemic parameters, such as hemorrhagic tendency and neutrophil level and function. REFERENCES 1. Barrett AP. Oral mucosal complications in cancer chemotherapy. Aust NZ J Med 1984;14:7-12. 2. Barrett AP. Gingival lesions in leukemia: a classification. J Periodontol 1984;55:585-8. 3. Barrett AP, Bilous AM. Oral patterns of acute and chronic graft-vs-host disease. Arch Dermatol 1984; 120: 1461-5. 4. Schubert MM, Sullivan KM, Morton TH, et al. Oral mani-
316
Barrett
Oral March,
festations of chronic graft-vs-host disease. Arch Intern Med 1984;144;1591-5. 5. Barrett AP. Oral complications of bone marrow transplantation. Aust NZ J Med 1986;16:239-40. 6. Barrett AP. Evaluation of nystatin in prevention and elimination of oropharyngeal Candida in immunosuppressed patients. ORAL
I.
8.
9. 10.
11.
12.
SURC
ORAL
MED
Barrett AP. A long-term cial herpes simplex virus
ORAL
PATHOL
1984:58:148-51.
prospective clinical study of orofainfection in acute leukemia. ORAL SURG ORAL MED ORAL PATHOL 1986;61:149-52. Barrett AP, Buckley DJ, Greenberg ML, Earl MJ. The value of exfoliative cytology in diagnosing oral herpes simplex infection in the immunosuppressed. ORAL SURG ORAL MED ORAL PATHOL 1986;62:175-8. Barrett AP. Patterns and significance of oral hemorrhage in acute leukemia. J Oral Med 1986;41:193-6. Stafford RF, Lockhart PB, Sonis AL, Sonis ST. Hematologic parameters as predictors of oral involvement in the presentation of acute leukemia. J Oral Med 1982;37:38-41. Dreizen S, McCredie KB, Keating MJ, Bodey GP. Oral infections associated with chemotherapy in adults with acute leukemia. Postgrad Med 1982;7 1: 133146. Friedreich N. Ein neuer Fall von Leukamie. Virchows Arch 1857;12:37-58.
13. Dreizen gingival ORAL
Surg. I987
S, McCredie KB, Keating MJ, Luna MA. Malignant and skin “infiltrates” in adult leukemia. ORAL SURG MED
ORAL
PATHOL
1983;55:572-9.
14. Forkner CE. Clinical and pathologic differentiation of the acute leukemias. Arch Intern Med 1934;53:1-34. 15. Dreizen S. Stomatotoxic manifestations of cancer chemotherapy. J Prosthet Dent 1978;40:650-5. 16. Barrett AP. Clinical characteristics and mechanisms involved in chemotherapy-induced oral ulceration. ORAL SURG ORAL MED ORAL PATHOL (in press). 17. Duffy JH, Driscoll EJ. Oral manifestations of leukemia. ORAL
SURG
ORAL
MED
ORAL
PATHOL
1958;11:484-90.
18. Lynch MA, Ship II. Oral manifestations of leukemia: postdiagnostic study. JADA 1967;75:1139-44. 19. Sonis A, Sonis S. Oral complications of cancer chemotherapy in pediatric patients. J Pedodont 1979;3: 122-8. Reprint requests to: Dr. A.P. Barrett Westmead Hospital Dental Clinical School Westmead, New South Wales, 2145, Australia
a
HOSPITAL
DENTAL
CLINICAL
Westmead, New South Wales, Australia SCHOOL
AND
DEPARTMENT
OF MEDICINE
Oral complications were detected during 89% of hospital admissions for treatment of acute leukemia in adults. Changes that reflected the underlying myelosuppression and general immunosuppression predominated. Hemorrhagic phenomena (77%), neutropenic ulceration (49%), and herpes simplex virus infections (39%) were the most common. (ORAL SURC. ORAL MED. ORAL PATHOL. 1987;63:313-6)
A
range of oral complications may occur during remission-induction therapy for acute leukemia. These may be classified according to whether they are a direct consequence of the leukemic process or of the chemotherapy used in its management, or whether they occur indirectly as a result of underlying myelosuppression and general immunosupression.l** This range of possible changes has been extended in allogeneic bone marrow transplantation to include oral manifestations of acute and chronic graft-versus-host disease.3-5 The aim of this prospective clinical study was to determine the range and incidence of oral complications that occurred in a group of patients who underwent intensive conventional chemotherapy for acute leukemia. MATERIALS AND METHODS
I examined forty-four adult patients with acute leukemia during 57 separate hospital admissions over a 42-month period. Patients were examined initially within 24 to 72 hours after their arrival at the hospital, before treatment commenced, and then were examined on a daily basis until they were discharged or died. All patients received intensive remission-induction chemotherapy for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). During a total of 47 admissions, those with AML (35 patients) received one or more courses of *Staff Specialist Clinical School.
(Oral
Diagnosis),
Westmead
Hospital
Dental
chemotherapy involving a three-drug combination of daunorubicin, cytosine arabinoside, and 6-thioguanine (DAT). Five of these patients also received acridinylanisidine (m-AMSA) after a poor response to DAT. Those with ALL (9 patients/ 10 admissions) were managed with combination therapy, including vincristine sulfate, prednisone, daunorubicin, cytosine arabinoside, asparaginase, 6-mercaptopurine, and methotrexate, supplemented with central nervous system radiotherapy. Clinical examination was supplemented (where applicable) with fungal, viral, and bacterial culture methods and exfoliative cytopathologic study.6-8 Patients were encouraged to maintain existing oral hygiene practices-or upgrade oral hygiene if necessary-and instructed to use a mouthwash of bicarbonate of soda in water followed by topical nystatin or amphotericin suspensions four times daily throughout their hospitalization.‘*6 Chemical antiplaque agents, such as chlorhexidine preparations, were not used in this study. RESULTS
The range and incidence of oral complications are shown in Table I; these are grouped according to a previously reported classification system.‘, * Oral changes were found during 89% of the admissions. Leukemic
infiltration
Three patients had overt signs of direct leukemic cell infiltration of oral tissues. Tonsillar infiltration, which resolved with effective chemotherapy, was 313
314
Barrett
Oral March.
Table I. Summary
Group* AML (N = 47) ALL (N = 10) Combined total (N = 57) *AML:
Acute
ttonsillar
myeloid
of oral complications
during 57 admissions for acute leukemia
Gingival or tonsillarf inJiltration
Drug-induced ulceration
2(4%) 1 (IO%)? 3 (5%)
2 (4%) 2 (20%) 4 (7%)
leukemia.
ALL:
Acute
lymphoblastic
Bruising and bleeding 41 (87%) 3 (30%) 44 (77%)
Herpes simplex infection
Neutropenic ulceration 26 (55%) 2 (20%) 28 (49%)
19 (40%) 3 (30%) 22 (39%)
Candidiasis 12 (26%) 5 (50%) 17 (30%)
1 ~$~%~f 8 (17%‘) I (10%) 9 (16%)
leukemia.
infiltration.
seen in one patient at initial presentation of ALL. In one patient AML (monocytic type) was diagnosed as such after the patient consulted a periodontist about gingival enlargement. This also resolved with effective chemotherapy. Profound gingival infiltration developed in another patient with AML (monoblastic type) in the terminal stages of his disease. Drug-induced
ulceration
Oral mucosal breakdown and ulceration as a direct consequence of drug toxicity were seen in only four patients. Ulceration was not seen in relation to DAT; however, extensive breakdown occurred in two of five patients who received m-AMSA after a poor response to- DAT. Two patients with ALL experienced methotrexate-induced ulceration; severe ulceration occurred in one after a single 15 mg intrathecal dose, and mild ulceration occurred in a second after a high-dose (750 mg) intravenous infusion. Predisposing factors were not apparent. Bruising
Surg. I987
and bleeding
Oral bruising and/or frank bleeding were observed during 77% of the admissions. This was more common during admissions for AML (41 of 47) than for ALL (3 of 10). Furthermore, only isolated petechiae and relatively minor ecchymoses were observed in patients with ALL. In contrast, multiple hemorrhagic bullae (25 of 41), frank bleeding from gingivae or mucosal lesions (10 of 41) and/or deep muscle and tissue plane hematomas (3 of 41) were also observed in patients with AML. The greater incidence and severity of oral bruising and bleeding in the AML group were a reflection of the greater overall degree and duration of thrombocytopenia seen in that group9 rather than a suggestion of impaired platelet function in AML (compared to ALL), as proposed by Stafford and colleaguesLo in one study. Neutropenic
ulceration
Neutropenic ulceration of the oral mucosa was common (49% of the admissions), and the incidence
was greater in the patients with AML (55%) than in those with ALL (20%). This appeared to be a reflection of the significantly greater degree and duration of neutropenia in the AML group. While all patients with AML experienced profound neutropenia (levels < lOO/mm’), only 50% of those with ALL did so. Furthermore, the duration of neutropenia (levels <1000/mm3) was longer in patients with AML (average: 48 days) than in those with ALL (average: 26 days). This was statistically significant (t test, p < 0.05). Herpes
simplex
virus infection
Orofacial mucocutaneous infection by herpes simplex virus was found in 22 of 57 (39%) admissions. Intraoral mucosal involvement occurred on 13 of 22 occasions. Acyclovir was administered to six patients by intravenous infusion (5 mg/kg body weight) at 8-hour intervals for 5 to 8 days; one patient promptly became afebrile, indicating that-in the absence of bone marrow recovery or changes to existing antibiotic therapy-the infection had disseminated. Candidiasis
Oropharyngeal candidiasis occurred in 17 (30%) patients. Poor patient compliance with topical antifungals and/or failure of nystatin to prevent colonization6 were implicated in all cases. In one patient with disseminated candidiasis at postmortem examination, systemic access from the oral cavity appeared likely through sites of colonized neutropenic ulceration. Bacterial
infections
Localized dental/periodontal infections occurred in seven patients. Despite repeated blood cultures, bacteria were not isolated from the peripheral circulation in any case. Five infections quickly resolved with intravenous benzylpenicillin, and the remaining two patients, who had gingival cellulitis,* responded to intravenous metronidazole. In another two patients, generally innocuous oral commensal bacteria (Leptotrichia buccalis in one case and Strepto-
Volume Number
63 3
Oral complications
coccus mitis in the second) were isolated on blood culture during febrile episodes. Systemic access appeared likely in both cases through sites of extensive oral neutropenic ulceration. Oral infections by opportunistic enteric pathogens-as described by Dreizen and colleagues”-were not seen. DISCUSSION
Friedreich12 (1857) is credited with the first detailed account of a patient who died of acute leukemia, with evidence of weakness, hemorrhagic tendency, hepatosplenomegaly, and oral ulceration. Since that time, oral mucosal complications in patients with leukemia-particularly acute leukemia-have become accepted as common features of the disease and its treatment. The results of the present study, in which one or more oral changes occurred in 89% of hospital admissions for acute leukemia, confirmed this. Leukemic infiltration of oral tissues was an uncommon finding in this study. This finding-that gingival infiltration occurred during only 2 of 57 (3.5%) admissions--corresponds with that of Dreizen and colleagues,‘3 who reported it in 38 of 1076 (3.6%) patients in their study. Furthermore, as observed by Dreizen13: (a) gingival infiltration was not confirmed to acute monocytic leukemia (of which it was originally considered pathognomonic’4) but occurred in the present study in a case of acute monoblastic leukemia and (2) local predisposing factors were not apparent. Drug-induced oral mucosal ulceration occurred during only four (7%) admissions and was unexpected in all four cases. As previously observed, predisposing factors were not identified.‘” I6 Considering the chemotherapeutic agents and administration, schedules used in this study are similar to those employed worldwide and, considering that the incidence of drug-induced ulceration was low (7%) compared to the overall incidence of oral changes (89%), clinicians should avoid dismissal of oral ulceration in these patients as simply drug-induced “mucositis” and should carefully consider other causes (e.g., neutropenic ulceration and herpes simplex infection) in the differential diagnosis of oral ulceration. More common than those oral mucosal changes that reflected the direct consequences of the leukemia and its management were those lesions that reflected the underlying myelosuppression and general immunosuppression. Hemorrhagic phenomena and neutropenic ulceration were the most common changes and occurred in 77% and 49% of admissions, respectively. In most earlier studies of oral changes in patients
during chemotherapy for acute leukemia
315
with acute leukemia, orofacial infection by herpes simplex virus has either not been reported or has been reported as uncommon-particularly oral mucosal involvement.“~ 17-19Recent studies including the present, however, indicate that these orofacial infections are indeed common in patients who received conventional chemotherapy for acute leukemia (39% admissions here) and may occur even more often in recipients of bone marrow transplantation (up to 60% of cases).4s7 This finding is probably primarily a result of an increasing awareness of the variability of clinical presentation of these infections in the immunosuppressed and increased use of specific diagnostic aids, such as exfoliative cytopatholoiitY*
I. 2. 1.8
Despite routine topical antifungal prophylaxis, clinical candidiasis occurred at some stage during 17 (30%) admissions. In the earlier phase of the study, this appeared to be principally a reflection on the limited ability of nystatin to eliminate and prevent candidal colonization of the oral cavity.6 In all cases where topical amphotericin B appeared ineffective, poor patient compliance was implicated, particularly in patients in the terminal stages of their disease. Apart from two patients with evidence of septicemia caused by oral commensals, oral bacterial infections in these patients appeared of minor local significance only. Aggressive orofacial mucocutaneous infections by enteric pathogens, of the type reported by Dreizen and colleagues,” were not found in any patient in this study. Where enteric pathogens were isolated from swabs of oral lesions (e.g., neutropenic ulceration), they appeared to be local contaminants only. They did not appear to alter the clinical characteristics of the various lesions in any way; nor were they seen to be related to septicemia in any case. In conclusion, oral complications are common (and frequently multiple) in patients who receive aggressive remission-induction chemotherapy for acute leukemia. Differentiation of the various oral changes in these patients through daily observations promotes early intervention of complications, such as herpes simplex virus and candidal infections, and provides the clinician with an ongoing indicator of systemic parameters, such as hemorrhagic tendency and neutrophil level and function. REFERENCES 1. Barrett AP. Oral mucosal complications in cancer chemotherapy. Aust NZ J Med 1984;14:7-12. 2. Barrett AP. Gingival lesions in leukemia: a classification. J Periodontol 1984;55:585-8. 3. Barrett AP, Bilous AM. Oral patterns of acute and chronic graft-vs-host disease. Arch Dermatol 1984; 120: 1461-5. 4. Schubert MM, Sullivan KM, Morton TH, et al. Oral mani-
316
Barrett
Oral March,
festations of chronic graft-vs-host disease. Arch Intern Med 1984;144;1591-5. 5. Barrett AP. Oral complications of bone marrow transplantation. Aust NZ J Med 1986;16:239-40. 6. Barrett AP. Evaluation of nystatin in prevention and elimination of oropharyngeal Candida in immunosuppressed patients. ORAL
I.
8.
9. 10.
11.
12.
SURC
ORAL
MED
Barrett AP. A long-term cial herpes simplex virus
ORAL
PATHOL
1984:58:148-51.
prospective clinical study of orofainfection in acute leukemia. ORAL SURG ORAL MED ORAL PATHOL 1986;61:149-52. Barrett AP, Buckley DJ, Greenberg ML, Earl MJ. The value of exfoliative cytology in diagnosing oral herpes simplex infection in the immunosuppressed. ORAL SURG ORAL MED ORAL PATHOL 1986;62:175-8. Barrett AP. Patterns and significance of oral hemorrhage in acute leukemia. J Oral Med 1986;41:193-6. Stafford RF, Lockhart PB, Sonis AL, Sonis ST. Hematologic parameters as predictors of oral involvement in the presentation of acute leukemia. J Oral Med 1982;37:38-41. Dreizen S, McCredie KB, Keating MJ, Bodey GP. Oral infections associated with chemotherapy in adults with acute leukemia. Postgrad Med 1982;7 1: 133146. Friedreich N. Ein neuer Fall von Leukamie. Virchows Arch 1857;12:37-58.
13. Dreizen gingival ORAL
Surg. I987
S, McCredie KB, Keating MJ, Luna MA. Malignant and skin “infiltrates” in adult leukemia. ORAL SURG MED
ORAL
PATHOL
1983;55:572-9.
14. Forkner CE. Clinical and pathologic differentiation of the acute leukemias. Arch Intern Med 1934;53:1-34. 15. Dreizen S. Stomatotoxic manifestations of cancer chemotherapy. J Prosthet Dent 1978;40:650-5. 16. Barrett AP. Clinical characteristics and mechanisms involved in chemotherapy-induced oral ulceration. ORAL SURG ORAL MED ORAL PATHOL (in press). 17. Duffy JH, Driscoll EJ. Oral manifestations of leukemia. ORAL
SURG
ORAL
MED
ORAL
PATHOL
1958;11:484-90.
18. Lynch MA, Ship II. Oral manifestations of leukemia: postdiagnostic study. JADA 1967;75:1139-44. 19. Sonis A, Sonis S. Oral complications of cancer chemotherapy in pediatric patients. J Pedodont 1979;3: 122-8. Reprint requests to: Dr. A.P. Barrett Westmead Hospital Dental Clinical School Westmead, New South Wales, 2145, Australia
a