[CANCER RESEARCH 26 Part 1, 1290-1296, June 1966] …The diagnosis of herpes zoster or varicella was made on find ing typical clinical signs and symptoms alone, whereas the diag nosis

[CANCER RESEARCH 26 Part 1, 1290-1296, June 1966]

Summary of Infectious Complications Occurring inPatients with Hodgkin's Disease

ALBERT R. CASAZZA, CHARLES P. DUVALL, AND PAUL P. CARBONE

Medicine Branch, National Cancer Institute, NIH, Hethesda, Maryland

Summary

The charts and autopsy protocols of 51 patients with Hodgkin's

disease were reviewed. Thirty-five patients were found to havesignificant infectious complications during their clinical course.The majority of these problems occurred during the last quarterof illness, when chemotherapy was ineffective. Bacterial infections, especially septicemia, were most frequent although arelatively large number of viral and fungal diseases were found.Single episodes of toxoplasmosis and pneumocystis were also

discovered in this series.Thirty-five of the 51 patients were infected at the time of

death ; however, infection per se could not be shown to adverselyaffect survival for the entire group. However, each of the 4 documented infections with cryptococcosis was primarily responsiblefor the death of the affected patients. Nevertheless, all patientshad active Hodgkin's disease at autopsy. No relationship ofinfection to various forms of therapy or to leukopenia was foundfor bacterial infections; however, 90% of the patients with fungaldisease and 100% of the patients with cytomegalic inclusiondisease received corticosteroids.

Introduction

Infections are frequently encountered during the course ofpatients with neoplastic diseases (5, 6, 22). Changing patterns ofbacterial diseases and increasing frequencies of fungal diseaseshave been reported, particularly in patients with acute leukemiasand malignant lymphomas (14, 16, 25). Moreover, infections dueto organisms with low pathogenicity for normal human adultshave been described (Refs. 8, 9, 16, 17, 25-27).

This report elucidates the frequency, type, and distribution ofinfections occurring during the course of patients with Hodgkin's

disease and examines the role of therapy and extent of diseasepredisposing to their development. Moreover, the relationshipof infection to mortality was investigated.

Materials and Methods

All charts of patients with Hodgkin's disease autopsied at theNIH during the years 1953-64 were reviewed. The number andtype of infectious episodes and the relation of these episodes to thecourse of disease, treatment, and hÃ©matologiestatus were examined. The clinical and autopsy findings were evaluated todetermine the cause of death.

An infectious episode was defined as an event of clinical signsand symptoms highly indicative of sepsis (i.e., chills, temperature

greater than 38Â°C,hypotension, pulmonary symptoms, etc.)

coupled with microbiologie documentation of bacterial and fungaldisease. In only 1 instance, a response to antibiotic therapy wasused as supporting evidence. An infection was considered presentif there was appropriate histopathologic evidence regardless ofthe presence or absence of cultural data. A positive heart bloodculture was interpreted in light of clinical and histopathologicdata.

The diagnosis of herpes zoster or varicella was made on finding typical clinical signs and symptoms alone, whereas the diagnosis of cytomegalic inclusion disease or disseminated herpessimplex was made usually with confirmatory histopathologic material.

Fifty-four charts were reviewed and 51 were found acceptablefor this study. Three were not included because of incompleteness.Nineteen patients were female, and 32 were male. The medianage at the time of biopsy was 33 years. The median survival fromthe time of biopsy (diagnosis) was 30 months (Table 1).

These 51 patients were classified as to the stage of disease (2)by the authors according to the clinical data presented in therecords (Table 1).

Results

Thirty-eight of the 51 patients surveyed experienced episodesof infection during the course of their neoplastic disease. Three ofthese 38 patients had infections which were adequately treatedand did not recur so that the infection had no role in the ultimatedemise of these patients. The remaining 35 patients had infections at autopsy. In 17 of these 35 patients the infections occurred prior to the terminal episode, whereas 18 became infectedonly during the last 1-10 days of life (Table 2). The median survival for the 2 groups of patients (i.e., those with and withoutdemonstrable infections at postmortem examination) was essentially the same (Table 2). All patients in this study populationhad active Hodgkin's disease demonstrated by autopsy, and no

patient died of infection alone while the diseae was in apparentremission. Five patients were considered to have died because ofinfection (Table 3).

T ijpes of Infection

All infectious episodes were categorized for the 35 patients withinfections at post mortem. The total number of infections was 86and the average number of infections per infected patient was 2.3(Table 4). Bacterial infections were most common in thisgroup of patient, caused the major portion of morbidity, and

1290 CANCER RESEARCH VOL. 20

on July 5, 2021. © 1966 American Association for Cancer Research. cancerres.aacrjournals.org Downloaded from

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Infectious Complications

TABLE 1 TABLE 4

No. of patientsRatio of females to malesMedian age in years (range)Median survival in months (range)Clinical staging at time of biopsy

Stage IStage II

AB

Stage IIINot defined

5119/3233 (6-71)30 (1-135)

125101521

4

TABLE 2

PatientcharacteristicsNo

infections (clinical orpostmortem)Clinicalinfections, none atpostmortemClinicaland/or postmorteminfectionTerminal

infectiononlyPreterminaland terminal133351817Mediansurvival(months)3230

TABLE

Causes of death

Hodgkin's disease aloneIlodgkin's disease and infection

Primarily Hodgkin's disease

Primarily infectionInfections alone

Xo. of patients

1635305(I

were associated most frequently with mortality. Nevertheless,viral, fungal, and rarer types of infections were noted for 30 ofthe 86 episodes. The distribution of the different types of infections is listed in Table 4. Mixed infections, i.e., bacterial andviral, bacterial and fungal, bacterial and miscellaneous, accountedfor nearly 30'o of the total number of infectious episodes.

Bacterial Infections

Septicemia occurred with surprising frequency in these patients and represented the most common manifestation of bacterial infection. Seventy-five % of these episodes were associatedwith a known primary site of infection. Table 5 depicts the frequencies of the different kinds of bacterial infections. HemolyticStaphylococcits aureus, Pseudomonas aeruginosa, and Escherichiacoli were the organisms most frequently associated with bloodstream invasion (Table 6). These same organisms were responsible for the majority of pneumonias. There was only 1 instanceof pneumococcal pneumonia.

Each of the 4 episodes of enteritis was associated with a strainof salmonella organisms. The usual pathogens were encounteredin the instances of urinary tract infections and skin abscesses. Allof the 3 ca.sesof empyema and most of the cases or urinary tractinfection were associated with structural abnormalities related tothe underlying Hodgkin's disease (e.g., fistulous eommunica-

Types ofinfectionsBacterialBacterial

aloneBacterialandotherViralViral

onlyViralandotherFungalFungal

onlyFungalandotherMiscellaneousToxoplasmaPneumocystisTuberculosisTotalNo.

ofepisodes/patientNo.of episodes/patient with infectionXo.

ofepisodes4979837111561710381.72.3

TABLE 5

Bacterial infections

SepticemiaPrimary site unknownPrimary site known

PneumoniasSkin abscessesLung and skinEmpyemaGastrointestinal tract

PneumoniaEnteritisUrinary tractSkin abscessesMiscellaneous

Total

Number

21105231

111

n444I

56

TABLE 6BACTERIALSEPTICEMIAS

Kind oforganismsHemolytic

SlaphylococcusaureusPseudomonassp.EscherichiacoliStreptococcussp.Klebsiellasp.Proteussp.ParacolonbacillusMixedGram-negativeHemolytic

Staphylococcus andGram-negativeTotalNumber3110552111429

JUNE 1966 1291



Albert R. Casazza, Charles P. Duvall, and Paul P. Carbone

TABLE 7

VIRAL INFECTIONS

Herpes zosterVaricellaCytomegalovirusHerpes simplex

Total

153

17

TABLE 9INFECTION CORRELATEDWITH DISEASE COURSE

TYPEBacterialViralFungalDISEASEQUARTER1st0102nd1003rd4524th2352TERMINALPERIOD2866TOTALEPISODES561710

TABLE 8

Infections Number

FungalDisseminatedCryptococcusHistoplasmaNocardiaLocalPulmonary

(Nocardia andCandida)Gastrointestinal(Candida)TotalMiscellaneousMycobacteriaToxoplasmaPneumocystis

cariniiTotal4112264101113

tions). Similarly, most of the episodes of skin abscesses wererelated to excoriations or the administration of intravenoustherapy.

Of the 5 patients with Hodgkin's disease who died primarily

of infection, only 1 died of bacterial diseaseâ€”staphylococcal

pneumonia. The remaining patients died of cryptococcal disease.

Viral Injections

There were 8 instances of herpes zoster and 1 case of adultvaricella in this group of patients (Table 7). These occurrenceswere not associated with mortality and therefore were not considered in analyzing the survival data. Nevertheless, 4 of the 5cases of cytomegalic inclusion disease and all the cases of disseminated herpes simplex were diagnosed only at postmortemexamination. One case of cytomegalovirus infection (CID) wasdiscovered by antemortem culture of saliva. Most CID infectionswere not implicated as major causes of demise; however, eachepisode of herpes simplex and one of CID were considered significant contributory factors to mortality. All of the patients withCID had coexisting infections. Four of these 5 had inclusionsin alveolar cells of the lungs. The presence of these inclusionswas considered to be clinically insignificant in producing diseasemanifestations except in 1 patient who had a hemorrhagic bron-

chopneumonia.

Fungal Infections

There were 6 cases of disseminated fungal infections and 4 otherpatients with localized fungal disease (Table 8). Each instanceof cryptococcal disease was felt to be the major cause of death.

Miscellaneous Infections

There were single cases of disseminated tuberculosis andtoxoplasmosis and pulmonary pneumocystitis encountered inthis series of patients. These infections caused major morbiditybut were considered not to be the primary cause of death. Thecase of tuberculosis was the only one in this group in which apositive diagnosis was made before death.

Clinical Correlations

Most of the infections occurred relatively late in the diseasecourse. To substantiate this hypothesis, the clinical course wasdivided into quarters. The terminal period was listed separatelyfrom the 4th quarter. The terminal period was defined as thatperiod (1-10 days before death) in which a sudden adverse turn

of events occurred leading to the death of the patient. Table 9shows the relative frequency of infections according to taxonomiegroup that occurred during the defined intervals. The preponderance of episodes occurred during the 4th quarter and with theterminal period.

Because chemotherapy and steroid therapy have been implicated as predisposing factors to infection (11, 30), the amountand type of therapy administered was charted according toquarters for both the infected and noninfected patients. As canbe seen in Chart 1, the proportion of patients receiving radiationtherapy and chemotherapy was relatively constant in each quarter for the infected group. On the other hand, the proportion ofpatients receiving radiation therapy decreased and the proportion receiving chemotherapy increased as the disease progressedfor the noninfected group (Chart 2). The proportion of patientsreceiving steroids increased significantly in the last quarter forboth groups.

Leukopenia (granulocytes less than 1000/cu mm) was not asignificant contributing factor to infection as only 4 of the 35infected patients had this degree of leukopenia during the terminal episode whereas 3 of the 16 noninfected patients experiencedthis degree of leukopenia within the last 10 days of life.

Although the median survival for both the noninfected groupand the infected group was similar, life-table analysis (Chart 3)

shows that the slope of the probability curve of survival for theinfected group was less than that for the noninfected groups afterthe point of median survival. Because the staging and histology

1292 CANCER RESEARCH VOL. 2(>




UJ <H o:< Lu

1.0

0.8

0.6LuO

tr oO uj

irO.

0.4

0.2

Radiotherapy

ChemotherapyCorticosteroidi

2nd 3rd 4thDISEASE QUARTER

CHART \. Correlation of therapy to the course of the disease in 25 patients with only bacterial infections at postmortem.

1.0 -

^.> 0.85$< uiu. *~o o2?O >

H UJir oo uiÃ¨* Â°2

0.6

0.4

Radiotherapy

Chemotherapy

Corticosteroids

2nd 3rd 4th

DISEASE QUARTER

CHART2. Correlation of therapy to the course of the disease in 16 patients without infection.

cr

1.0

0.8

0.6

5 Â°4OD

CO

Â§ 0.2CL

Survival :o infected - 35 Patientsâ€¢Unmfected - 16 Patients

10 20 30 40 50 60 70

DISEASE DURATION (Months)

CHART3. Life-table analysis: probability curves.

80 90 100

JUNE 1966 1293




TABLE 10SURVIVALANDTYPE OF INFECTIONS

Survival group(months)g30>30Xon-infectedpatients88Infectedpatients1910Bacterial158Fungal02Bacterialand fungal34Other12

of both groups was similar, the difference in slope implies thatinfection did not affect survival adversely.

The infected category of patients was then separated into 2subgroups according to survival. Table 10 shows the distributionof the various types of infection in those patients surviving upto the median time and those living longer. Two points are apparent. Of those 19 patients dying with infection after a briefcourse of Hodgkin's disease, 15 died with only a bacterial in

fection, whereas those dying after a relatively prolonged illnesswere prone to have fungal disease as well as bacterial infections.There was only 1 instance of disseminated fungal disease (histo-plasmosis) in the 19 patients living 30 months or less, whereasthere were 5 instances of disseminated fungal disease in the 16patients living longer than 30 months. All 4 episodes of crypto-coccosis occurred in patients surviving longer than 30 months.The mean survival of these patients so infected was 92 months(median 102 months).

The mean survival of the 5 patients with CID was 27 months(median 30 months). The episodes of toxoplasmosis and pneumo-cystis occurred in patients with longer survivals.

Discussion

Infection has been recognized as a major cause of morbidityand mortality in patients with hÃ©matologiemalignancies (14,25). Bacterial and fungal diseases have been frequently associatedwith acute leukemia (14, 30), chronic lymphatic leukemia (4,21), multiple myeloma (10), and lymphomas with hypogamma-globulinemia (31). Herpes zoster, tuberculosis, and fungal diseases, especially cryptococcosis, have been described as commoncomplications of patients with Hodgkin's disease (1, 5, 12, 16,

28). In the present report, 35 of 51 patients were found to havesignificant clinical infections during their disease course. Bacterial infection occurred as the only infectious complication in15 of 19 patients surviving less than 30 months, whereas mixedbacterial and fungal or virus was more prevalent in those patients living more than 30 months. As has been reported, herpeszoster and cryptocoeeal infections were important causes ofmorbidity and/or mortality in 12 of 51 patients. Tuberculosiswas noted in only 1 patient. Eighteen patients had more than 1infectious episode during their clinical course. Of the 86 occurrences of infection, 25 were mixed, involving more than 1 type oforganism.

Certain features of these infections are of interest. Unlike thesecondary hypogammaglobulinemic states (10, 31), Hodgkin's

disease does not seem to be punctuated with episodes of infectionduring the course of illness. The overwhelming majority of infections occurred during the last quarter of illness, and 33% ofpatients had a single infection associated with the terminal epi

sode. Moreover, 33% of patients with multiple infections contracted infectious disease during the last 12% of the clinicalcourse. Five of these 17 patients had local structural abnormalities which were considered significant etiologic factors.

Although I of patients were infected at autopsy, no adverseeffect of infection on survival could be demonstrated either bycomparing the median survival of infected and noninfectedgroups or by analyzing the probability of survival from life-table analysis (Chart 3). It must be emphasized that all patientshad active Hodgkin's disease at autopsy.

Several investigators have reported the high propensity ofpatients with leukemia or lymphoma to develo]) staphylococcal orGram-negative sepsis (14, 22, 30). Hersh et al. (16) have shownthat pseudomonas septicemia is becoming more frequent andstaphylococcal septicemia less frequent as a cause of death inacute leukemia. Our results confirm this as septicemia was themost frequent type of bacterial infection and hemolytic Staphi/lo-coccus aureus, E. coli, and Pseudomonas aeruginosa were the organisms most frequently responsible. However, the rising incidence of pseudomonas septicemia was not seen in this small groupof patients. An unusual association of salmonella infections withHodgkin's disease has been Â«'porteti by Heineman el al. (13)

and confirmed by this study, as 4 episodes of salmonella enteritiswere discovered in this group of patients.

Herpes zoster occurred with an incidence of 16%. This is higherthan the range of 3-8 c/0reported elsewhere (5, 28). There was

only 1 case of partial alopecia and facial scarring secondary toherpes zoster. The other episodes were self-limited without seriousmorbidity. One episode of mild varicella was recorded. Two patients with significant herpes simplex infections had severe ulcerative esophagitis. In 1 patient, there was extension to thetongue, larynx, and bronchi, with an extensive herpetic broncho-pneumonia. In addition there was associated candida esophagitisand active Toxoplasma condii subacute necrotizing encephalitisand focal myocarditis. This case has recently been reported ingreater detail (7).

Cytomegalic inclusions were fountl in 10% of cases. The lungswere involved in 4 of the 5 cases. Although cytomegalie inclusionpneumonia is a frequent cause of morbidity in patients undergoing renal homotransplantation (15), inclusion pneumonitis wasfelt to be significant in only 1 patient. A preliminary studypublished elsewhere by the present authors indicates thatthe salivary gland virus can be recovered from approximately3390 of adult patients with hÃ©matologiemalignancies.1 In thosepatients, as in these, the symptomotology and pathophysiologyof this infection are obscure.

In reviewing the cases of adult Pneumocystis carinii infections,28 instances of this infection were discovered (Refs. 26, 32; C. P.Duvall, unpublished review). Six cases were associated withHodgkin's disease, and 2 with other types of lymphoma. Al

though coexistent cytomegalie inclusion disease was found in 8of the 29 instances, no patient in this present series had boththese infections. Although Pneumocystis carinii pneumonitis wassuspected clinically in the 1 case described herein, diagnosis wasnot made until autopsy.

Toxoplasmosis must be recognized also as a complicatingfeature of Hodgkin's disease. The clinical and pathologic findings

have been reported in greater detail (7). In this instance, thecorrect diagnosis was made at postmortem examination; however,

1294 CANCER RESEARCH VOL. 26




in at least 1 other instance (8), a correct clinical diagnosis wasmade and effective therapy was given.

Hodgkin's disease has been reported as the type of lymphoma

most frequently associated with fungal disease (16). The intrinsic nature of Hodgkin's disease, adrenal eorticoid therapy, and

chemotherapy have been reported as factors which predispose toand account for the increased incidence of fungal diseases inthese patients (11, 16, 17, 29). The 20% incidence noted in thisgroup correlates well with that reported in the literature (19).

Special mention must be made of the cryptococcal infectionsencountered in this report. Although the cryptococcus organismis a pathogenic organism under usual circumstances, it seems toassume increased virulence when attacking patients with Hodgkin's disease. The resulting disease is usuali}' more widely dis

seminated (33), and this was corroborated by this study. Thisinfection was considered the primary cause of death in eachinstance encountered during this study. Two of the 4 patientshad substantial doses of amphotericin, while 1 died shortly afterdiagnosis and 1 case escaped clinical detection. Hutter andCollins, however, have reported good results in treating 16 casesof cryptococcus with amphotericin B (16).

Patients with Hodgkin's disease usually have normal 7-globu-

lin levels. However, decreased antibody production, delayedhomograft rejection, and impaired delayed hypersensitivityresponses are manifestations of the primary immunologie defectsencountered in this disease (2, 3, 18). A retrospective report suchas this cannot evaluate such features. This study seemed toindicate that the role of radiotherapy, chemotherapy, andsteroid therapy in predisposing these patients to infection wasrelatively minor. The patients who were not infected receivedrelatively more radiotherapy and chemotherapy than those withbacterial infection, whereas both groups received a similaramount of steroids. All the patients with CID and 90';c withfungal diseases received steroids during the course of illness.

It is to be noted that patients with structural abnormalitiesdue to the neoplastic disease behaved like those with localizedcarcinomas and developed multiple infections (20).

Almost all infections occurred when the neoplasm was faradvanced and no longer responsive to chemotherapy. This is tobe contrasted with earlier periods of active disease during whichthe patients were notably free of infection. Successful management of these infections requires effective antineoplastic chemotherapy, accurate diagnosis, and specific therapy of the infectiouscomplication. If the disseminated neoplastic disease cannot becontrolled, the patient usually will either die with the initialinfection or with a subsequent episode occurring shortly thereafter. Examination of the skin and lungs, detection of localmechanical defects, and serial blood cultures should providevaluable information for most bacterial infections. Antibiotictherapy when administered in the absence of known etiologicfactors must be geared to combat the high incidence of staphy-lococcal and Gram-negative bacillar}- disease. Such a program

might include methicillin and colistin.Unexplained clinical deterioration in the absence of proven

bacterial disease should alert the physician to the possibility offungal infections, particularly for those patients with diseaseduration in excess of 30 months. All but 2 of the fungal infections present in this series involved either the lungs, blood,meninges or a combination of these sites. Amphotericin li despite

its considerable nephrotoxicity, remains the agent of choice fortreating cryptococcosis, histoplasmosis, eandidiasis, and asper-gillosis. Nocardia can be treated with sulfonamides (27).

Similarly, establishing the diagnosis in the rare cases of pneu-mocystis and toxoplasmosis is of moni than academic importanceas a new agent, pentamidine isothionate, may be effective forthe former (23, 24) and sulfonamides are useful for the latter(8). There is no therapy available for disseminated cytomegalicinclusion disease; however, trials of various antiviral agents inanimals are in progress, and in vitro trials utilizing tissue culturetechnics are planned.

References

1. Aisenberg, A. C. Studies on Delayed Hypersensitivity inHodgkin's Disease. J. Clin. Invest., 41: 1964-70, 1962.

2. â€” â€”. Hodgkin's Diseaseâ€”Prognosis, Treatment, and Etio

logic and Immunologie Considerations. New Engl. J. Med.,270: 508-14, 565-70, 617-22; 1964.

3. Aisenberg, A. C., and Leskowitz, S. Antibody Formation inHodgkin's Disease. Ibid., 268: 1269-72, 1963.

4. Aroesty, J. M., and Furth, F. W. Infection and Chronic Lymphatic Leukemia, a Review of 61 Cases. N. Y. State J. Med.,6&: 1946-52, 1962.

5. Beeson, P. B., and McDermott, W. (eds.), Cecil and LoebTextbook of Medicine. Philadelphia: W. B. Saunders & Co.,1963.

0. Boggs, D. R., and Frei, E. Clinical Studies of Fever and Infection in Cancer. Cancer, IS: 1240-53, 1960.

7. Cheever, A. W., Valsamis, M. P., and Rabson, A. S. Necrotiz-ing Toxoplasmic Encephalitis and Herpetic Pneumonia Complicating Treated Hodgkin's Disease. New Engl. J. Med.,272: 26-29, 1965.

8. Connolly, C. S. Hodgkin's Disease Associated with Toxoplasmacondii. Arch. Internal Med., /12: 393-96, 1963.

9. Duvall, C. P., Casazza, A. R., Grimley, P. M., Carbone, P. P.,and Howe, W. P. Recovery of Cytomegalovirus from Adultswith Neoplastic Disease. Ann. Internal Med., 64: 531-41, 1966.

10. Fahey, J. L., Scoggins, R., Utz, J. P., and Szwed, C. F. Infection, Antibody Response and damma (Â¡lobulin Componentsin Multiple Myeloma and Macroglobulinemia. Am. J. Med.,35: 698-707, 1963.

11. Frenkel, J. K. Role of Corticosteroids as Predisposing Factorsin Fungal Diseases. Lab. Invest., //.- 1192-1208, 1962.

12. Gendel, B. R., Ende, M., and Norman, S. L. Cryptococcosisâ€”A Review with Special Reference to Apparent Association withHodgkin's Disease. Am. J. Med., 9: 343-55, 1950.

13. Heineman, H. S., Jensen, W. N., Cooper, W. M. and Brande,A. I. Hodgkin's Disease and Salmonella typhimurium Infection.J. Am. Med. Assoc., 188: 632-34, 1964.

14. Hersh, E. M., Bodey, G. P., Nies, B. A., and Freireich, E. J.Causes of Death in Acute Leukemia. Ibid., 193: 105-9, 1965.

15. Hill, R. B., Rowlands, D. T. and Rifkind, D. Infectious Pulmonary Disease in Patients Receiving ImmunosuppressiveTherapy for Organ Transplantation. New Engl. J. Med., 871:1021-27, 1964.

16. Hutter, R. V. P., and Collins, H. S. The Occurrence of Opportunistic Fungus Infections in a Cancer Hospital. Lab. Invest.,//: 1035-45, 1962.

17. Hutter, R. V. P., Lieberman, P. H., and Collins, H. S. Asper-gellosis in a Cancer Hospital. Cancer, 17: 747-56,1964.

18. Kelly, W. D., Lamb, D. L., Varco, R. L., and Good, II. A. AnInvestigation of Hodgkin's Disease with Respect to the Prob-

JUNE 1966 1295




lem of Homotransplantation. Ann. N.Y. Acad. Sci., 87: 187-202, 1900.

19. Keye, J. D., and Magee, W. E. Fungal Disease in a GeneralHospital, a Study of 88 Patients. Am. J. Clin. Pathol., #6:1235-53, 1950.

20. Kuschner, M., and Thomas, L. Infection in DisseminatedNeoplastic Disease. Bull. N. Y. Acad.Med., 33: 684-92, 1957.

21. Miller, D. G., and Karnofsky, D. A. Immunologie Factors andResistance to Infection in Chronic Lymphatic Leukemia.Am. J. Med., 31: 748-57, 1961.

22. Miller, S. P., and Shanbrom, E. Infections Syndromes of Leu-kemias and Lymphomas. Am. J. Med. Sci., Â¡46:420-28, 1963.

23. Bobbins, J. B., Miller, R. H., Arean, V. M., and Pearson, H. A.Successful Treatment of Pneumocystis carinii Pneumonitis ina Patient with Congenital Hypogammaglobulinemia. NewEngl. J. Med., 872: 708-13, 1965.

24. Rodgers, T. S., and Haggle, M. H. K. Pneumocystis cariniiPneumonia Associated with Hypogammaglobulinemia Responding to Pentamidine. Lancet, /: 1042, 1964.

25. Rogers, D. E. The Changing Pattern of Life ThreateningMicrobial Disease. New Engl. J. Med., 261: 677-83, 1959.

26. Rubin, E., and Zak, F. G. Pneumocysiis carinii Pneumonia inthe Adult. Ibid., 262: 1315-17, 1960.

27. Saltzman, H. A., Chick, E. W., and Conant, N. F. Nocardiosisas a Complication of Other Diseases. Lab. Invest., //: 1110-

17, 1902.28. Shanbrom, E., Miller, S., and Haar, H. Herpes Zoster in

HÃ©matologieNeoplasias: Some Unusual Manifestations. Ann.Internal Med., 53: 523-33, 1960.

29. Sheldon, W. H., and Bauer, H. The Role of Predisposing Factors in Experimental Fungus Infections. Lab. Invest., 11:1184-91, 1962.

30. Silver, 11. T., Utz, J. P., Frei, E., and McCullough, N. B.Fever, Infection and Host Resistance in Acute Leukemia.Am. J. Med., 2Â¿-25-39, 1958.

31. Ultmanii, J. E., Fish, W., Osserman, E., and Gellhorn, A.The Clinical Implications of Hypogammaglobulinemia inPatients with Chronic Lymphatic Leukemia and Lympho-cytic Lymphosarcoma. Ann. Internal Med., 51: 501-16, 1959.

32. White, W. F., Saxton, H. M., and Dawson, I. M. P. Pneumocystis Pneumonia. Brit. Med. J., 2: 1327-31, 1961.

33. Zimmerman, L. E., and Rappaport, H. Occurrence of Crypto-coccosis in Patients with Malignant Disease of Reticuloendo-thelial System. Am. J. Clin. Pathol., 84:1050-72, 1954.

129(5 CANCER RESEARCH VOL. 26



1966;26:1290-1296. Cancer Res Albert R. Casazza, Charles P. Duvall and Paul P. Carbone Hodgkin's DiseaseSummary of Infectious Complications Occurring in Patients with

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[CANCER RESEARCH 26 Part 1, 1290-1296, June 1966] …The diagnosis of herpes zoster or varicella was made on find ing typical clinical signs and symptoms alone, whereas the diag nosis