Melanoma as a subsequent neoplasm in adult survivors of childhood cancer: a report from the childhood cancer survivor study.

BACKGROUND: Childhood cancer survivors have a sixfold increased risk of developing subsequent neoplasms when compared to the general population. We sought to describe the occurrence of melanoma as a subsequent neoplasm among adult survivors of childhood cancer. PATIENTS AND METHODS: Among 14,358 5-year survivors of childhood cancer diagnosed between 1970 and 1986, we calculated the cumulative incidence, standardized incidence ratio (SIR), and absolute excess risk (AER) of subsequent melanoma. Potential risk factors were assessed using a cause-specific hazards model. RESULTS: Fifty-seven melanomas (46 invasive, 2 ocular, and 9 in situ) occurred in 51 survivors. The median time to the development of melanoma was 21.0 years (range: 5.6-35.4 years) and the median age at melanoma was 32.3 years (range: 10.9-49.0 years). Initial cancer diagnoses included soft tissue and bone sarcoma (n = 15), leukemia (13), lymphoma (14), central nervous system malignancy (5), Wilms tumor (3), and neuroblastoma (1). The cumulative incidence of first subsequent melanoma at 35 years from initial cancer diagnosis was 0.55% [95% confidence interval (CI): 0.37-0.73]. The SIR of subsequent invasive malignant melanoma of the skin was 2.42 (95% CI: 1.77-3.23), and the AER was 0.10 (95% CI: 0.05-0.15) per 1,000 person-years. No statistically significant associations were found between melanoma risk and family history of cancer, demographic, or treatment-related factors. CONCLUSION: Survivors of childhood cancer have an approximate 2.5-fold increased risk of melanoma. Early screening and prevention strategies are warranted.

Breast-feeding and risk of childhood acute leukemia.

BACKGROUND: Breast-feeding is well known to have a protective effect against infection in infants. Although the long-term effects of breast-feeding on childhood cancer have not been studied extensively, a protective effect against childhood Hodgkin's disease and lymphoma has been suggested previously from small investigations. In this study, we tested the hypothesis that breast-feeding decreases the risk of childhood acute leukemia. METHODS: A total of 1744 children with acute lymphoblastic leukemia (ALL) and 1879 matched control subjects, aged 1-14 years, and 456 children with acute myeloid leukemia (AML) and 539 matched control subjects, aged 1-17 years, were included in the analysis. Information regarding breast-feeding was obtained through telephone interviews with mothers. All leukemias combined, histologic type of leukemia (ALL versus AML), immunophenotype of ALL (early pre-B cell, pre-B cell, or T cell), and morphology of AML were assessed separately in the data analysis. RESULTS: Ever having breast-fed was found to be associated with a 21% reduction in risk of childhood acute leukemias (odds ratio [OR] for all types combined = 0.79; 95% confidence interval [CI] = 0.70-0.91). A reduction in risk was seen separately for AML (OR = 0.77; 95% CI = 0.57-1.03) and ALL (OR = 0.80; 95% CI = 0.69-0.93). The inverse associations were stronger with longer duration of breast-feeding for total ALL and AML; for M0, M1, and M2 morphologic subtypes of AML; and for early pre-B-cell ALL. CONCLUSION: In this study, breast-feeding was associated with a reduced risk of childhood acute leukemia. If confirmed in additional epidemiologic studies, our findings suggest that future epidemiologic and experimental efforts should be directed at investigating the anti-infective and/or immune-stimulatory or immune-modulating effects of breast-feeding on leukemogenesis in children.

Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study.

BACKGROUND: Because survival rates among childhood cancer patients are increasing, assessing the risk of second and subsequent malignant neoplasms (SMNs) is ever more important. Using the Childhood Cancer Survivor Study cohort, we identified the risk of SMNS: METHODS: A retrospective cohort of 13 581 children diagnosed with common cancers before age 21 years and surviving at least 5 years was constructed with the use of data from patients treated at 25 U.S. and Canadian institutions. SMNs were ascertained through self-administered questionnaires and verified by pathology reports. Information on therapeutic exposures was abstracted from medical records. The risk of SMN was evaluated by standardized incidence ratios (SIRs) and excess absolute risk. Poisson multiple regression models were used to assess the impact of host and therapy factors on the risk of developing SMNS: All statistical tests were two-sided. RESULTS: In 298 individuals, 314 SMNs were identified (SIR = 6.38; 95% confidence interval [CI] = 5.69 to 7.13). The largest observed excess SMNs were bone and breast cancers (SIR = 19.14 [95% CI = 12.72 to 27.67] and SIR = 16.18 [95% CI = 12.35 to 20.83], respectively). A statistically significant excess of SMNs followed all childhood cancers. In multivariate regression models adjusted for therapeutic radiation exposure, SMNs of any type were independently associated with female sex (P<.001), childhood cancer at a younger age (P for trend <.001), childhood Hodgkin's disease or soft-tissue sarcoma (P<.001 and P =.01, respectively), and exposure to alkylating agents (P for trend =.02). Twenty years after the childhood cancer diagnosis, the cumulative estimated SMN incidence was 3.2%. However, only 1.88 excess malignancies occurred per 1000 years of patient follow-up. CONCLUSIONS: Success in treating children with cancer should not be overshadowed by the incidence of SMNS: However, patients and health-care providers must be aware of risk factors for SMNs so that surveillance is focused and early prevention strategies are implemented.

Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study.

PURPOSE: Survivors of childhood and adolescent cancer are at risk for long-term effects of disease and treatment. The Childhood Cancer Survivor Study assessed overall and cause-specific mortality in a retrospective cohort of 20,227 5-year survivors. PATIENTS AND METHODS: Eligible subjects were individuals diagnosed with cancer (from 1970 to 1986) before the age of 21 who had survived 5 years from diagnosis. Underlying cause of death was obtained from death certificates and other sources and coded and categorized as recurrent disease, sequelae of cancer treatment, or non-cancer-related. Age and sex standardized mortality ratios (SMRs) were calculated using United States population mortality data. RESULTS: The cohort, including 208,947 person-years of follow-up, demonstrated a 10.8-fold excess in overall mortality (95% confidence interval, 10.3 to 11.3). Risk of death was statistically significantly higher in females (SMR = 18.2), individuals diagnosed with cancer before the age of 5 years (SMR = 14.0), and those with an initial diagnosis of leukemia (SMR = 15.5) or CNS tumor (SMR = 15.7). Recurrence of the original cancer was the leading cause of death among 5-year survivors, accounting for 67% of deaths. Statistically significant excess mortality rates were seen due to subsequent malignancies (SMR = 19.4), along with cardiac (SMR = 8.2), pulmonary (SMR = 9.2), and other causes (SMR = 3.3). Treatment-related associations were present for subsequent cancer mortality (radiation, alkylating agents, epipodophyllotoxins), cardiac mortality (chest irradiation, bleomycin), and other deaths (radiation, anthracyclines). No excess mortality was observed for external causes (SMR = 0.8). CONCLUSION: While recurrent disease remains a major contributor to late mortality in 5-year survivors of childhood cancer, significant excesses in mortality risk associated with treatment-related complications exist up to 25 years after the initial cancer diagnosis.

Treatment of intermediate risk rhabdomyosarcoma and undifferentiated sarcoma with alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide.

Over 50% of patients with newly diagnosed rhabdomyosarcoma (RMS) are in the 'intermediate risk' group with a 3-year progression-free survival of approximately 65%. This group consists of stage 1, group III, non-orbit tumours; stage 2, group II and III; and all stage 3 patients utilising the Intergroup Rhabdomyosarcoma Study (IRS) staging system. The role of doxorubicin in the treatment of RMS has been controversial. Ifosfamide, both alone and in combination with etoposide, has significant activity in patients with RMS. The aim of this pilot study was to examine the efficacy and toxicity of a chemotherapy regimen of alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide for intermediate risk RMS. 30 patients with intermediate risk RMS or undifferentiated sarcoma (US) were treated with alternating cycles of vincristine/doxorubicin/cyclophosphamide (VDC) and etoposide/ifosfamide (EI) at planned intervals of 3 weeks. Local treatment of the tumour in most cases was performed after four cycles of chemotherapy, followed by an additional 10 cycles of chemotherapy. At a median follow-up of 37.5 months, the Kaplan-Meier estimate of 3-year event-free survival was 85% (95% confidence interval 72-99%). The overall survival at 3 years was 91% (95% confidence interval 80-100%). No patient died from toxicity. The most common toxicity was febrile neutropenia in 35% of VDC and 26% of EI cycles. No nephrotoxicity or cardiac toxicity was seen. No patient progressed prior to week 12 local therapy. Alternating cycles of VDC and EI are an effective treatment for patients with intermediate risk RMS and US. Toxicity is tolerable. Delaying local treatment until week 12 does not compromise outcome.

Invasive Scopulariopsis in the immunocompromised host.

Opportunistic infections with fungal organisms have been well described in patients undergoing intensive chemotherapy and bone marrow transplantation. In two patients, invasive infections with the saprophyte Scopulariopsis developed either following intensive chemotherapy or bone marrow transplant. Fungal disease persisted in both patients despite resection of the primary focus and prolonged treatment with the usual antifungal agents, and contributed to the death of one patient.

Autologous bone marrow transplantation in acute myeloid leukemia: the University of Minnesota experience.

PURPOSE: To report the outcome of autologous bone marrow transplantation for patients with acute myeloid leukemia (AML) in first or greater complete remission (CR) treated by autologous bone marrow transplantation using two different preparatory regimens. METHODS AND MATERIALS: Between September 1986 and August 1993, 75 patients with AML ranging in age from 6 months to 58 years underwent autologous bone marrow transplantation using previously harvested and frozen unpurged (n = 6) or 4-hydroperoxycyclophosphamide purged marrows (n = 69). Patients were in first CR (n = 44) or beyond first CR (n = 31). The preparative regimen consisted of 120 mg/kg of cyclophosphamide (CY) and 1320 cGy total body irradiation (TBI) in eight fractions over 4 days (CY/TBI) in 29 patients; and 16 mg/kg of Busulfan (BU) and 200 mg/kg of CY (BU/CY) in 46 patients. Thirty-five of these 75 patients (18 CY/TBI and 17 BU/CY) were part of a randomized trial comparing the two preparative regimens. RESULTS: At 2 years, overall survival and disease-free survival (DFS) were 49% [95% confidence interval (C.I.) 37-61%] and 43% (95% C.I. 32-55%), respectively. Patients in first CR had a significantly better outcome than patients beyond first CR with an estimated 2-year DFS of 59% (95% C.I. 44-74%) vs. 21% (95% C.I. 5-36%, log-rank p = 0.0001), respectively. For patients conditioned with CY/TBI, the estimated 2-year DFS was 52% compared to 39% for BU/CY (log-rank p = 0.35). Estimated 2-year relapse rates were 44% vs. 56% (log-rank p = 0.40), respectively. For patients in first CR, no differences in DFS were observed between the two regimens (2-year estimates 69% vs. 55% log-rank p = 0.52). Patients beyond first CR had a significantly improved DFS with the CY/TBI regimen (2-year estimates of 38% vs. 7%, log-rank p = 0.04). No differences were found between the two regimens in terms of time to WBC engraftment, absolute neutrophil count of > 500, incidence of bacteremias, or median time to hospital discharge. Interstitial pneumonitis developed in two patients (one BU/CY, one CY/TBI) and venoocclusive disease developed in seven BU/CY patients (Fishers exact test p = 0.04). CONCLUSIONS: For patients beyond first CR, the CY/TBI regiment provided a better outcome, with a significantly better disease-free survival and less venoocclusive disease. For patients in first CR, no significant difference between the two regimens was found. The high relapse rate, especially for patients with advanced disease, emphasizes the need for early transplantation and for new strategies to improve outcome.

Randomized comparison of cyclophosphamide-total body irradiation versus busulfan-cyclophosphamide conditioning in autologous bone marrow transplantation for acute myeloid leukemia.

PURPOSE: This prospective trial of autologous bone marrow transplantation for acute myeloid leukemia was undertaken to compare the outcome using two different preparative regimens. METHODS AND MATERIALS: Between October 1987 and April 1993, 35 patients with acute myeloid leukemia in first (n = 12) or greater (n = 23) remission were stratified by remission status and randomized to undergo 4-hydroperoxycyclophosphamide purged autologous bone marrow transplantation after either cyclophosphamide (120 mg/kg) and total body irradiation (1320 Gy in eight fractions over 4 days) (CY/TBI), or busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) (BU/CY) conditioning. RESULTS: At 2 years, overall survival and disease-free survival were 39% (95% confidence intervals (CI) 22-57%) and 36% (95% CI 19-52%), respectively. Patients in first complete remission had a significantly better outcome with a 2-year disease free survival of 57% (95% CI 28-86%) compared to others at 24% (95% CI 6-43%, log rank p = 0.048). For patients conditioned with CY/TBI, the estimated 2-year disease-free survival was 50% compared to 24% for patients conditioned with BU/CY (log rank p = 0.12). Estimated 2-year relapse rates were 43% vs. 70% (log rank p = 0.17), respectively. For patients in first complete remission no differences in disease-free survival (2-year estimates 67% vs. 50%, log rank p = 0.69), between the two regimens were observed. For patients in greater than first complete remission there was a trend towards improved disease-free survival in the CY/TBI arm (2-year estimates 42% vs. 9%, log rank p = 0.06). There were no differences in time to white blood cell count (WBC) engraftment, absolute neutrophil count of > 500, incidence of bacteremias, or median time to hospital discharge between the two regimens. Acute toxicities were similar. Interstitial pneumonitis developed in two patients (one on each arm), while veno occlusive disease developed in three BU/CY patients, but none of the CY/TBI patients (log rank p = 0.07). CONCLUSIONS: Cyclophosphamide-total body irradiation provided an equivalent or better outcome to BU/CY, particularly in advanced patients, and should remain the standard by which new regimens are judged. The high relapse rate with both regimens, especially patients who were in greater than in first complete remission, emphasizes the need for early transplant and for new strategies to improve outcome.

Tics and vocalizations in children treated with carbamazepine.

Three patients are reported who, following the initiation of carbamazepine therapy for seizure control, either experienced the onset of Tourette's syndrome or a worsening of their tics and vocalizations. Blood levels of carbamazepine were within the therapeutic range, and no patient showed clinical signs of intoxication. Tics and vocalizations did not resolve following discontinuation of carbamazepine therapy. Carbamazepine may trigger the onset of Tourette's syndrome in susceptible patients.

Retinoblastoma and Hirschsprung disease in a patient with interstitial deletion of chromosome 13.

Retinoblastoma is a rare pediatric malignancy (1/20,000) while Hirschsprung disease is a relatively common pediatric disorder (1/5,000). We describe a boy with bilateral retinoblastoma, Hirschsprung disease, multiple minor anomalies, and an interstitial deletion 13q (q13 --> q22). This child and a similar previously reported girl with retinoblastoma and Hirschsprung disease may represent a previously unrecognized contiguous gene syndrome.

Patterns of gonadal dysfunction following bone marrow transplantation.

We reviewed gonadal function in 270 patients who underwent bone marrow transplantation (BMT) between 1974 and 1988. Age at transplant ranged from 6 to 54 years (mean 25.6 years). Diagnoses included acute myelogenous leukemia, chronic myelogenous leukemia, aplastic anemia, acute lymphoblastic leukemia, non-Hodgkin lymphoma, Hodgkin's disease and other diagnoses. Effects of patient characteristics on risk of gonadal dysfunction were analyzed by comparing the cumulative probability of developing gonadal dysfunction over time from BMT. Ninety-two percent of the males and 99% of the females developed evidence of gonadal dysfunction. Females were not only more likely to develop elevated gonadotrophin levels than males, but did so earlier after BMT. Odds ratios were calculated to determine potentially important prognostic factors for the development of an elevated gonadotrophin level. Older age at BMT was correlated with an increased risk in the development of elevated gonadotrophin levels. Individuals who received radiation were more likely to develop an elevated FSH level over time than those who had received no preparative radiation treatment. Males were more likely to experience gonadal recovery than females. In those cases that did recover, males tended to recover more quickly after BMT than females.

Successful bone marrow transplantation for severe aplastic anemia following orthotopic liver transplantation: long-term follow-up and outcome.

Severe aplastic anemia (SAA) is well described in children following liver transplantation for fulminant hepatic failure (FHF) secondary to non-A, non-B, non-C hepatitis, and is associated with a high mortality rate. Successful immunosuppressive treatment of SAA following liver transplantation has been reported, but death from infectious complications is not uncommon. We report the 8-year follow-up of a 3.5-year-old boy who underwent successful HLA-identical sibling donor bone marrow transplant for SAA 7 months following orthotopic liver transplant for non-A, non-B, non-C hepatitis. His post-bone marrow transplantation course was uneventful with no evidence of liver toxicity. Eight months following BMT he developed renal cell carcinoma metastatic to lymph nodes which was treated surgically. Six years following BMT he developed a mucoepidermoid carcinoma of the parotid gland also treated surgically. Despite these malignancies, he is currently well 8 years following liver and bone marrow transplantation, without signs of GVHD, growth failure or liver graft rejection. This is the first report of long-term follow-up of bone marrow transplantation for SAA following liver transplantation. The occurrence of two subsequent malignancies in this child underscores the need for close follow-up of future similar cases.

Outcomes following mechanical ventilation in children undergoing bone marrow transplantation.

Between 1976 and 1992, 869 patients <19 years of age underwent BMT at the University of Minnesota for a variety of malignant and non-malignant disorders. One hundred and ninety-six required mechanical ventilation (MV) at some time from the start of pre-BMT cyto reduction through the first year following BMT. Reasons for MV included respiratory compromise, upper airway management and non-pulmonary indications for respiratory support. In multivariate models, underlying diagnosis, receipt of HLA-mismatched marrow and the presence of acute graft-versus-host disease (aGVHD) were independent predictors of the need for MV. Indication for MV, underlying diagnosis, and presence of aGVHD were independent predictors of successful extubation. Overall survival at 2 years was 14% among MV patients and 52% among non-MV patients. While the need for MV during BMT reduces the overall likelihood of survival, 40% of children who required MV were successfully extubated; 35% of these extubated patients were long-term survivors. This outcome is better than that reported for adult BMT patients requiring respiratory support, who show survival of <5% at 6 months following BMT. Our data suggest extrapolation of outcome data from adult to pediatric patients is not appropriate and aggressive care of pediatric patients requiring respiratory support is not futile.

Cardiovascular function in children following bone marrow transplant: a cross-sectional study.

Sixty-three patients who had undergone a BMT at age < or = 18 years were evaluated cross-sectionally to determine cardiac function as well as the long-term prevalence, types, severity, and risk factors of cardiac abnormalities. Patients were > or = 1 year post-BMT and were evaluated by history, resting ECG, echocardiography (ECHO), exercise treadmill test, chest X-ray, pulmonary function tests and review of past cardiac studies. Patients were assigned a New York Heart Association (NYHA) class based on an activity and cardiac symptoms questionnaire. Pretransplant preparative regimens included high-dose cyclophosphamide (CY) and total body/lymphoid irradiation (n = 38), CY in combination with other chemotherapy (n = 22), and other drug combinations (n = 3). Forty patients (63.5%) had received prior anthracyclines (median 307 mg/m2). Patients' ages ranged from 1.9 to 32 years (median 10.9 years) with median follow-up of 3.3 years (range 1-16.3 years). Twenty-six patients (41.3%) had a cardiac abnormality detected at follow-up. In 21 patients the abnormal finding had not been present at the pre-BMT evaluation. Ten patients (16.4%) had resting ECG abnormalities. Left ventricular ejection fraction (LVEF) by ECHO was mildly decreased to 50-54% in three patients and markedly decreased to 40% in one patient. Only one patient (1.7%) developed a mildly abnormal shortening fraction of 27%. All patients with ECHO abnormalities were asymptomatic. Twenty-three of 31 patients > or = 9 years of age (74%) who underwent a treadmill exercise test had a borderline or abnormal response to exercise. There was no correlation between demographic factors, previous therapy, preparative regimen or length of follow-up with the post-BMT ECG, ECHO and treadmill abnormalities. Overall, eight patients (12.7%) were symptomatic and NYHA class II or III, and all had abnormal exercise tests. The presence of symptoms and NYHA class were predictors for oxygen consumption during exercise (P = 0.03 and 0.02, respectively) and tended to predict overall treadmill results also. Late cardiac abnormalities do occur following BMT in childhood and thus, there is a clear need for continued, serial long-term cardiac evaluation in transplant survivors. Evaluations should include exercise stress testing to detect inadequate cardiac output as well as oxygen consumption during exercise.

The relation of Langerhans cell histiocytosis to acute leukemia, lymphomas, and other solid tumors. The LCH-Malignancy Study Group of the Histiocyte Society.

The frequency of Langerhans cell histiocytosis (LCH) and a malignant neoplasm occurring in the same individual appears to be greater than previously recognized. To define the occurrence and the pattern of these events, a Study Group of the Histiocyte Society initiated a registry of patients in whom this association occurred synchronously or asynchronously. Evaluation of 54 patients detected two patterns of associations between LCH and other disorders. First, it is possible that therapy of LCH promotes a secondary malignancy. Second, it is possible that a genetic predisposition, with or without the immunosuppression associated therapy for the malignancy, plays a role in the development and expression of disseminated LCH. Data collected by the LCH-Malignancy Study Group may provide insights into the etiology and pathophysiology of LCH.

Delayed cerebrovascular complications of intrathecal colloidal gold.

OBJECTIVE: Therapy with intrathecal colloidal gold has been used in the past as an adjunct in the treatment of childhood neoplasms, including medulloblastoma and leukemia. We describe the long-term follow-up period of a series of patients treated with intrathecal colloidal gold and emphasize the high incidence of delayed cerebrovascular complications and their management. METHODS: Between 1967 and 1970, 14 children with posterior fossa medulloblastoma underwent treatment at the University of Minnesota. Treatment consisted of surgical resection, external beam radiotherapy, and intrathecal colloidal gold. All patients underwent long-term follow-up periods. RESULTS: Of the 14 original patients, 6 died within 2 years of treatment; all experienced persistent or recurrent disease. The eight surviving patients developed significant neurovascular complications 5 to 20 years after treatment. Three patients died as a result of aneurysmal subarachnoid hemorrhage, and five developed ischemic symptoms from severe vasculopathy that resembled moyamoya disease. CONCLUSION: Although therapy with colloidal gold resulted in long-term survival in a number of cases of childhood medulloblastoma, our experience suggests that the severe cerebrovascular side effects fail to justify its use. The unique complications associated with colloidal gold therapy, as well as the management of these complications, are presented. We recommend routine screening of any long-term survivors to exclude the presence of an intracranial aneurysm and to document the possibility of moyamoya syndrome.

Late effects of treatment in children with cancer.

For most children, cancer has become a curable disease. With this increased survival, the late effects of the diagnosis of cancer and its therapy have assumed increased importance for these children. Multiple late effects of essentially all organ systems have been described in selected groups of survivors. These may be modified by patient characteristics as well as therapy. Continued definition of these late sequelae are of critical importance to both the survivor of childhood cancer as well as the physicians planning future therapies.

Epidemiology of the childhood acute leukemias.

Epidemiologic studies of the childhood leukemias have provided information relevant to several aspects of the care and follow-up of these children. The observations made regarding in utero radiation and ALL risk have certainly curtailed the use of routine obstetric diagnostic radiographs; observations regarding the association between birth weight, fetal loss, and other gestational events provide added enthusiasm for further research into basic biologic events occurring during fetal development; and the genetic patterns of disease supply critical information for genetic counseling and follow-up of affected patients and families. Additionally, the continued epidemiologic surveillance of children with cancer serves to form the foundation from which we will assess any future changes in childhood cancer incidence or pattern. Although not discussed here, the epidemiology of late effects, including second malignancies, reproductive function, and neuropsychologic functioning will assume a more prominent role as more children survive ALL and move into adulthood. While analytic studies have yet to yield an association as strong as the lung cancer/cigarette association in adults, future research designed to isolate biologically homogeneous disease populations for study may lead us to new and important associations. The continued cooperation of large pediatric oncology groups and private physicians is crucial as these future investigations are undertaken.

Impact of surgical treatment on paranasal fungal infections in bone marrow transplant patients.

Invasive fungal sinusitis can develop in immunosuppressed patients. A more complex problem is immunosuppressed patients who have undergone bone marrow transplantation. For a prolonged period, they are both neutropenic and thrombocytopenic. Survival in these patients is poor, and the role for extensive surgical intervention for sinus disease has to be weighed against the risk and the potential that this is a systemic disease. Between January 1983 and June 1993, 29 bone marrow transplant recipients with documented invasive fungal infections of the sinuses and paranasal tissues required surgical intervention. This represents 1.7% of the total 1692 bone marrow transplants performed. There were 22 allogeneic, 6 autologous, and 3 unrelated donor transplants, with two patients receiving two separate grafts. Underlying diseases included 24 hematologic malignancies and 5 other disorders, including 1 aplastic anemia and 1 solid tumor. The mortality rate from the initial fungal infection was 62%. Twenty-seven percent resolved the initial infections but subsequently died of other causes. All patients received medical management, such as amphotericin, rifampin, and colony-stimulating factors, in addition to surgical intervention. Surgical management ranged from minimally invasive procedures to extensive resections including medial maxillectomies. Sixty-one percent of the patients who died of the initial infection had undergone extensive surgical procedures versus 55% of those who resolved the infection. Recovery of neutrophil counts was required to clear the infection but did not necessarily predict a good outcome because 50% of those who died of the infection had experienced neutrophil recovery. White blood cell counts at the time of surgery were not significantly different between the two groups. Prognosis was poor when cranial and orbital involvement and/or bony erosion occurred.