Prognosis is extremely poor for AML patients who relapse after allogeneic stem cell transplantation. Donor Lymphocyte infusions (DLI) can be used to salvage these patients with complete response rates reported to be 10-15% with an associated 40-60% chance of developing clinically significant GVHD. The mechanism by which DLI results in clinical responses is thought to be a T-cell mediated process. Data suggest that DLI normalizes the T-cell receptor repertoire and expands the anti-leukemic cell population. Hypomethylating agents, which appear to foster the graft versus leukemia phenomenon, were combined with DLI in attempt to enhance the graft versus leukemia effect. We report ten AML patients who received Decitabine +/- Etoposide with incremental DLI as salvage after relapse from allogeneic stem cell transplantation during the years 2007-2010. These patients were between the ages of 26- 73 years. Six patients had de novo AML. Three patients were transformed from MDS, and one from essential thrombocythemia. Eight patients had reduced intensity conditioning regimens. Two patients received a fully ablative preparative regimen. Average time to progression post transplant was 17 months. Patients received Decitabine at 20mg/m2 for 5 - 10 days, some in combination with Etoposide for 3-5days for disease control. Patients received 1-4 courses of treatment approximately every 28 days with DLI between days 14-21. Two patients who progressed while receiving Decitabine/Etoposide received Clofarabine at 20-52mg/m2 for 5 days, with subsequent DLI. Cell dose ranged from 1.27 to 31.7 CD3+ cells / kg. Two patients received a mobilized DLI. Six out of ten patients regained full chimerism. One patient who relapsed with extra medullary disease never lost his graft. Seven out of ten patients achieved a complete remission. Only one patient developed Grade 2 GVHD of the skin. Overall survival in these patients after relapse from allogeneic transplantation was 10.8 months. The combination of Decitabine and DLI is a well tolerated outpatient therapeutic option for patients with relapsed AML post allogeneic stem cell transplantation. The majority of patients regained full chimerism and achieved complete remission with little or no GVHD.

Abstract Background: Genetic diseases may display parent-of-origin effects. In such cases, the risk depends on the specific parent or origin allele. Imprinting effect is evident in autosomal dominant hereditary paraganglioma leads to tumors only if inherited from paternal germline. Cancer penetrance in mutations carriers may be determined by the parent origin of BRCA mutation. Methods: From 2007–2010 we analyzed 1889 consecutive (136 ovarian + 1753 breast) breast (BrCa) or ovarian cancer (OvCa) patients presenting for treatment at our outpatient facility. In 130 patients with BRCA 1 or 2 mutations the parent of origin for the mutation was known. Of the 130 patients 2 had both BRCA1 and BRCA2 mutated paternally inherited and were excluded from this analysis. Of the breast cancer patients: 28 patients had paternal and 29 had maternal BRCA1 mutations, 24 had paternal and 21 had maternal BRCA 2 mutations. Of the ovarian cancer patients 6 had paternal and 10 had maternal BRCA1 mutations, 7 had paternal and 3 had maternal BRCA2 mutations. In carriers of BRCA mutations the mean age at diagnosis for ovarian cancer was 51 (range 21–70) and for breast cancer was 43 (range 24–78). Two-sample t-test was used to compare the mean age at diagnosis in patients with BRCA 1 or 2 mutations of paternal or maternal inheritance. For breast cancer maternal allele versus paternal allele 2-sample t-test and p-value were compared for the age at first diagnosis. For breast cancer patients BRCA1 maternal inheritance (mean+SD yrs) 45.73+11.22 versus paternal inheritance 38.04+7.14 2-sample t-test p-value p<0.0020. For breast cancer BRCA2 maternal inheritance (mean+SD yrs) 50.65+10.44 versus paternal inheritance 41.68+6.16, 2-sample t-test p-value p<0.0008. Results: Significantly younger age at breast cancer diagnosis was observed in paternal vs. maternal inheritance of BRCA1 mutation (38 vs 46, respectively, p<0.0020) and BRCA2 mutation (42 vs 51 respectively, p<0.0008). There was no significant difference between paternal and maternal age of ovarian cancer diagnosis of BRCA1 (p<0.1415) or BRCA2 mutation (p<0.3470). Conclusion: The restrospective nature of the study may introduce ascertainment bias. However, the breast and ovarian cancers cases in BRCA1 & 2 carriers with maternal or paternal inheritance mirror the Mendelian autosomal dominant pattern in our unselected consecutive cohort of patients. Maternal and paternal inherited BRCA alleles may not be exchangeable. Women with paternally inherited mutations in BRCA gene mutations develop breast cancer at younger age compared with women who inherit the gene mutations from their mothers. In this small sample, clear differences at age of cancer diagnosis are apparent in paternal inheritance of BRCA gene mutation. If this observation duplicates in larger cohorts results will have important implications for recommendation of surgical risk reduction in BRCA mutation carriers. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-13-02.

1547 Background: Inherited mutations in autosomal dominant genes account for 5-10% of breast and colon cancers. Benefits of appropriate genetic testing and counseling have been well determined. If referral patterns for genetic counseling differ by disease, many patients may be underserved. In the diverse population that we serve, we endeavored to understand which patients are referred for genetic testing by disease-specific risk. Methods: Over a 5-year period (2004–2009) we analyzed genetic test resultsby referral source and mutation in 1,193 consecutively testedindividuals (excluding those with who had been previously tested at our institution to limit the bias for mutation positivity). Results: Of these 1,193 individuals seen for genetic counseling and testing at our institution, 1,129 subjects were referred for the presumptive diagnosis of HBOC, and 64 were referred for either a presumptive diagnosis of Lynch syndrome (n = 59) or with multiple colorectal polyps (n = 5). As in the Table, of the 1,129 subjects referred for the presumptive diagnosis of HBOC, 162 (14%) had deleterious mutations in either BRCA 1 or BRCA 2 genes. Of the 64 subjects referred with CCS, 30 (46%) were found to have deleterious mutations. A marked difference in referral patterns was found by disease presumed risk in terms of the number of patients seen. Additionally, a much higher rate of positive mutations was found in those with CCS, indicating a higher threshold for referral for these patients compared with those with HBOC, despite a similar incidence at our center of breast and colorectal cancers. Conclusions: Barriers to genetic testing exist, especially with CCS. To overcome this problem, enhanced education and outreach efforts to the medical community and to patients is needed if the established benefits of genetic testing and counseling are to be realized. No. (% referral) % with mutations (95% CI) % of total cancer diagnosis at our center % of total cancer diagnosis in the US HBOC 1,129 (94%) 14% (12%–16%) 19% 14% (27% in women) CCS 64 (6%) 47% (35%–59%) 15% 10% No significant financial relationships to disclose.

We report 40 patients (pts) with AML who underwent autologous HSCT in first (CR1) or second (CR2) remission from 2002 to 2007. Twenty one were male and nineteen were female with a mean age of 52.8 (range 35–66) years. Patients enrolled in clinical trials are not included in this analysis. Using CALGB (Byrd) criteria, 6 had favorable cytogenetic risk (all in CR2), 26 had intermediate risk, including 22 with normal karyotypes (20 in CR1 and 2 in CR2), and 8 had unfavorable cytogenetics (7 in CR1 and 1 in CR2), including two patients with t(9;22). One pt had Ph+ AML and one CML with myeloid blast crisis. One patient had AML transformed from myelodysplastic syndrome (MDS). Four patients had AML with multi-lineage dysplasia (MLD). Nine patients were in CR2. Thirty-five patients had intensification / mobilization with high dose VP16/ARAC, four with high dose ARAC and one patient had a bone marrow harvest. Thirty-six patients received Busulfan (0.8mg/kg x 16 doses) and VP-16 (60mg/kg) as their preparative regimen. Four received Busulfan (0.8 mg/kg x 16 doses) and Cytoxan (120 mg/kg). One hundred day transplant related mortality was 2.5%. Mean overall survival was 20.9 months. Mean disease free survival was 36.7 months with a range of 10–76 months. One year overall survival was 63%, with a one year disease free survival of 40%. Four of six pts with favorable cytogenetics are alive in CR more than 24 months after autologous transplant. Two patients with t(9;22) are on imatinib maintenance in CR 12 and 42 months post transplant. One patient with APL developed a secondary MDS with a monosomy 7. No patients with prior MDS or MLD were alive after 12 months. Five patients who relapsed after autologous HSCT went on to receive reduced intensity allogeneic transplantation with a 100 day mortality of 0%. We conclude that autologous HSCT should be considered an effective and safe post-remission consolidation therapy for pts with intermediate risk AML in CR1 and for pts with favorable cytogenetics in CR2. Patients with MLD and prior MDS do poorly. Prior autologous HSCT does not increase the 100 day mortality with reduced intensity allogeneic transplantation. Further studies are necessary, continuing to focus on risk-adapted therapy and assessing quality of life endpoints. We report 40 patients (pts) with AML who underwent autologous HSCT in first (CR1) or second (CR2) remission from 2002 to 2007. Twenty one were male and nineteen were female with a mean age of 52.8 (range 35–66) years. Patients enrolled in clinical trials are not included in this analysis. Using CALGB (Byrd) criteria, 6 had favorable cytogenetic risk (all in CR2), 26 had intermediate risk, including 22 with normal karyotypes (20 in CR1 and 2 in CR2), and 8 had unfavorable cytogenetics (7 in CR1 and 1 in CR2), including two patients with t(9;22). One pt had Ph+ AML and one CML with myeloid blast crisis. One patient had AML transformed from myelodysplastic syndrome (MDS). Four patients had AML with multi-lineage dysplasia (MLD). Nine patients were in CR2. Thirty-five patients had intensification / mobilization with high dose VP16/ARAC, four with high dose ARAC and one patient had a bone marrow harvest. Thirty-six patients received Busulfan (0.8mg/kg x 16 doses) and VP-16 (60mg/kg) as their preparative regimen. Four received Busulfan (0.8 mg/kg x 16 doses) and Cytoxan (120 mg/kg). One hundred day transplant related mortality was 2.5%. Mean overall survival was 20.9 months. Mean disease free survival was 36.7 months with a range of 10–76 months. One year overall survival was 63%, with a one year disease free survival of 40%. Four of six pts with favorable cytogenetics are alive in CR more than 24 months after autologous transplant. Two patients with t(9;22) are on imatinib maintenance in CR 12 and 42 months post transplant. One patient with APL developed a secondary MDS with a monosomy 7. No patients with prior MDS or MLD were alive after 12 months. Five patients who relapsed after autologous HSCT went on to receive reduced intensity allogeneic transplantation with a 100 day mortality of 0%. We conclude that autologous HSCT should be considered an effective and safe post-remission consolidation therapy for pts with intermediate risk AML in CR1 and for pts with favorable cytogenetics in CR2. Patients with MLD and prior MDS do poorly. Prior autologous HSCT does not increase the 100 day mortality with reduced intensity allogeneic transplantation. Further studies are necessary, continuing to focus on risk-adapted therapy and assessing quality of life endpoints.

Pituitary Apoplexy (PA) is an uncommon neurologic event that results from sudden hemorrhage or infarction of the pituitary gland. Most of these events occur in patients with undiagnosed pituitary adenoma. There are various precipitating causes. We report a case of PA precipitated by thrombocytopenia during autologous stem cell transplantation. The patient is a 48M with history of stage II multiple myeloma initially treated with lenalidomide and dexamethasone. The patient then proceeded to Auto PSCT. His preparative regimen consisted of melphalan 200 mg/m2. Initial lab values showed a platelet count of 429K/ul. The patient became febrile on Day 4 and was started on broad spectrum antibiotics. Voriconazole replaced fluconazole when fevers persisted. On Day 7, the patient complained of blurry vision. This was the first day plts were below 10K/ul. A possible culprit was voriconazole and it was discontinued. The patient complained his peripheral vision was particularly compromised, and bitemporal hemianopsia was confirmed. CT of the brain revealed a 2.3 × 2.5 cm hemorrhagic pituitary mass. Platelets were transfused to keep plts above 75K/ul. Hydrocortisone was begun, as was desmopressin, for developing diabetes insipidus. MRI confirmed a large suprasellar mass consisitent with a pituitary macroadenoma that contained hemorrhage. The incidence of PA with pituitary adenoma is variable, but has been reported to be as high as 27.7%. Many patients have nonfunctional adenomas or are asymptomatic prior to the event. Clinical symptoms of PA are also variable but the most common symptoms include headache, nausea, and visual deficits. As in most cases, our patient had an undiagnosed pituitary adenoma and was asymptomatic. The thrombocytopenia and immunocomprimise of PSCT can make the pituitary vulnerable to hemorrhage and abscess, both reported causes of apoplexy. Surgical management can be delayed by pancytopenia or other complications of PSCT. Transsphenoidal surgery has been shown to be more successful in improving vision if performed within 8 days of diagnosis. Emergent surgery is indicated for deteriorating vision, hemiparesis, or altered consciousness, while those with stable or resolving visual field deficits can be managed conservatively. Our patient was managed conservatively until engraftment. Transsphenoidal surgery was then performed, 9 days after diagnosis. At six months follow-up, his visual deficits had resolved but he continued to have diabetes insipidus.

Autologous stem cell transplantation has become the gold standard for treatment of patients with multiple myeloma under the age of 65, and improves survival for these patients. It is evident that all patients will progress after transplantation. At this time it is not clear what is the best induction regimen prior to high dose chemotherapy and ASCT. Thalidomide has been proven to impact on plasma cell growth through multiple mechanisms. At our institution we used thalidomide (50-100 mg) after ASCT as a maintenance program along with a bisphosphonate (Zometa or Aredia). We reviewed 68 myeloma patientswho were transplanted at our facility between 2001 and 2005. 30 patients were placed on a thalidomide maintenance program. Patients received various cytoreductive regimens prior to stemcell collection. 27 patients who received thalidomide were in partial remission prior to ASCT; 3 patients were in complete remission and none were refractory. Of the 38 patients who did not receive maintenance 35 were in partial remission, 2 were in complete remission and 1 was refractory. All patients except 2 received a preparative regimen including melphalan 200 mg per meter squared. 24 patients received thalidomide maintenance with 100 mg daily and 6 patients received 50 mg daily. The dose given depended on prior tolerability of the drug and history. Thalidomide was started between 120 and 150 days post ASCT. Patients needed to have an ANC above 1000 and platelets above 100 as well as resolution of transplant related toxicities. 13 patients needed a decrease in thalidomide because of neuropathy. One of these 13 patients also suffered from decreased GI motility and bezoar. The average time to progression was 32.5 months in the thalidomide group and 19 months in the patients who did not receive the drug. Patients who received thalidomide after transplant had improved median time to progression (36 months) compared to patients who did not receive thalidomide (15 months). Low dose thalidomide maintenance in combination with bisphosphonates seemed to improve progression free survival in myeloma patients after stem cell transplantation.

It is estimated that 80% of patients who undergo high-dose chemotherapy plus or minus radiotherapy prior to transplantation develop mucositis. Mucositis is a painful complication, which can lead to poor nutrition, increased use of narcotics, dehydration, greater risk for infection and bacteremia, as well as altered quality of life. Patients can have oral ulceration, epigastric discomfort, diarrhea, rectal irritation, and bleeding. It is likely that the complications of mucositis can contribute to increased lenght of stay during stem cell transplantation.The purpose of this study is to compare patients who received Kepivance(palifermin) as part of their treatment with patients that did not receive this medication during autologous stem cell transplantation. We performed a retrospective analysis of 70 patients; 20 prior to the institution of Kepivance(palifermin), and 50 patients after. The preparative regimens include Melphalan, Busulfan & Etoposide, Cytoxan, BCNU, Etoposide, and Busulfan & Cytoxan.The average length of stay for non-Kepivance patients was 32.3 days compared to 28 days in patients who received the drug. The severity of both oral and GI mucositis appeared to be less. 85% of non-Kepivance patients experienced diarrhea or rectal irritation, versus 52% with Kepivance. Neutropenic fever was noted in 95% of patients that did not receive the drug and 76% of the patients that did. There was a trend torward earlier engraftment in the Kepivance group.Kepivance seems to have had a positive effect on our patients. This updated study suggests an improvement in mucositis symptoms with the use of Kepivance(palifermin). It appears that mucositis and its treatment contribute to the length of stay and costs of stem cell transplantation. Qualtiy of life for these patients can be greatly improved if mucositis is reduced during the course of stem cell transplantation. It is estimated that 80% of patients who undergo high-dose chemotherapy plus or minus radiotherapy prior to transplantation develop mucositis. Mucositis is a painful complication, which can lead to poor nutrition, increased use of narcotics, dehydration, greater risk for infection and bacteremia, as well as altered quality of life. Patients can have oral ulceration, epigastric discomfort, diarrhea, rectal irritation, and bleeding. It is likely that the complications of mucositis can contribute to increased lenght of stay during stem cell transplantation. The purpose of this study is to compare patients who received Kepivance(palifermin) as part of their treatment with patients that did not receive this medication during autologous stem cell transplantation. We performed a retrospective analysis of 70 patients; 20 prior to the institution of Kepivance(palifermin), and 50 patients after. The preparative regimens include Melphalan, Busulfan & Etoposide, Cytoxan, BCNU, Etoposide, and Busulfan & Cytoxan. The average length of stay for non-Kepivance patients was 32.3 days compared to 28 days in patients who received the drug. The severity of both oral and GI mucositis appeared to be less. 85% of non-Kepivance patients experienced diarrhea or rectal irritation, versus 52% with Kepivance. Neutropenic fever was noted in 95% of patients that did not receive the drug and 76% of the patients that did. There was a trend torward earlier engraftment in the Kepivance group. Kepivance seems to have had a positive effect on our patients. This updated study suggests an improvement in mucositis symptoms with the use of Kepivance(palifermin). It appears that mucositis and its treatment contribute to the length of stay and costs of stem cell transplantation. Qualtiy of life for these patients can be greatly improved if mucositis is reduced during the course of stem cell transplantation.

Background: The clinical course of multiple myeloma is often associated with significant bone disease. Bisphosphonates have been shown to reduce the number of skeletal events. Treatment is continued even after hematopoietic progenitor cell transplant. Studies have shown renal toxicity associated with different bisphosphonates. Methods: We retrospectively reviewed the records of all multiple myeloma patients who underwent hematopoietic progenitor cell transplantation and received bisphosphonates during the period January 2001 to June 2004 at our institution. A total of 22 patients were analyzed. The types of bisphosphonates used were zolendronate and pamidronate. Patients were categorized as to the type of bisphosphonate used and age. Renal dysfunction was defined as an increase in serum creatinine of> 0.5 mg/dL over baseline. Results: Five of the 22 patients (22.7%) developed renal dysfunction. The table shows the distribution of patients, type of bisphosphonate, and the distribution of patients with renal toxicity. Among the 5 patients who developed renal impairment, 4 patients (80%) completely recovered their renal function and continued to use bisphosphonates. Conclusions: The analysis shows that bisphosphonates can be safeley used in multiple myeloma patients who have undergone hematopoietic progenitor cell transplant. If renal dysfunction develops during treatment, then the bisphosphonate can be discontinued temporarily. Renal function is likely to recover, and the bisphosphonate can be safely reimplemented.Table 1All Patients Who Received Bisphosphonates by Type and Age (1/2001- 6/2004)Age GroupZometaArediaZometa and ArediaTotal30–39000040–49402650–59411660–69531970–79001180+0000Total00022Renal Impairment by Age and Type of Bisphosphonate in Transplanted Multiple Myeloma Patients30–39000040–49101250–59000060–69020270–79001180+0000Total1225 Open table in a new tab

Diagnosis of active Human Herpesvirus 6 (HHV-6) infection in Hematopoietic Progenitor Cell (HPC) recipients can be difficult because the virus is ubiquitous and persistent in the human body. HHV-6 infection usually occurs within 2 to 4 weeks following transplantation. Infection with HHV-6 can be primary infection or reactivation. Viral infection can result in clinical symptoms including fever, rash, pneumonia, bone marrow suppression, encephalitis and rejection. There is also a possible correlation between graft versus host disease and HHV-6. We report a case of a 50 year old male with a history of refractory Acute Myelogenous Leukemia (AML). The patient was induced with Etoposide, Ara-C and Daunorubicin. He relapsed despite consolidation chemotherapy with HiDAC and Etoposide. He underwent other inductions without lasting response. Bone marrow biopsy after Myelotarg and HiDAC was hypocellular and he was taken directly to transplantation. The patient underwent a 5/6 HLA mismatched sibling donor transplant. The preparative regimen included Fludarabine 25 mg/m2/d × 5, Melphalan 70 mg/m2/d × 2 and ATG. His GVHD prophylaxis included Cyclosporine and Methotrexate. The patient engrafted on day 23. Donor chimerism was 100% on day 30. Approximately 3 weeks after transplant, the patient developed fever, severe myoclonus, mental status changes and amnesia. A brain MRI showed temporal lobe enhancement. Lumbar puncture revealed total protein of 58 mg/dL, glucose 80 mg/dL, WBC 1/μL, and RBC 1940/μL. HHV-6 IgG was 1:320 and IgM was negative prior to transplantation. The patient required intubation and blood pressure support. He was treated with IVIG weekly and Acyclovir initially. Multiplex RT-PCR analysis (Argene, Inc.) of the CSF was positive for HHV-6. The patient was started on ganciclovir when the data was obtained; however his status had improved prior to the change in medications. Follow-up HHV-6 titers 4 weeks after decompensation revealed HHV-6 IgG 1:1280. The patient developed grade 2–3 GVHD of the gut approximately day 55. Based on the MRI findings, the PCR positivity of the spinal fluid and the amnesia, we suspect that this is active HHV-6 infection. There have been several cases of encephalitis due to HHV-6 in HPC transplant patients who have presented with amnesia and who have temporal enhancement on MRI. HHV-6 can be a serious pathogen in HPC recipients receiving reduced-intensity preparative regimens. Diagnosis of active Human Herpesvirus 6 (HHV-6) infection in Hematopoietic Progenitor Cell (HPC) recipients can be difficult because the virus is ubiquitous and persistent in the human body. HHV-6 infection usually occurs within 2 to 4 weeks following transplantation. Infection with HHV-6 can be primary infection or reactivation. Viral infection can result in clinical symptoms including fever, rash, pneumonia, bone marrow suppression, encephalitis and rejection. There is also a possible correlation between graft versus host disease and HHV-6. We report a case of a 50 year old male with a history of refractory Acute Myelogenous Leukemia (AML). The patient was induced with Etoposide, Ara-C and Daunorubicin. He relapsed despite consolidation chemotherapy with HiDAC and Etoposide. He underwent other inductions without lasting response. Bone marrow biopsy after Myelotarg and HiDAC was hypocellular and he was taken directly to transplantation. The patient underwent a 5/6 HLA mismatched sibling donor transplant. The preparative regimen included Fludarabine 25 mg/m2/d × 5, Melphalan 70 mg/m2/d × 2 and ATG. His GVHD prophylaxis included Cyclosporine and Methotrexate. The patient engrafted on day 23. Donor chimerism was 100% on day 30. Approximately 3 weeks after transplant, the patient developed fever, severe myoclonus, mental status changes and amnesia. A brain MRI showed temporal lobe enhancement. Lumbar puncture revealed total protein of 58 mg/dL, glucose 80 mg/dL, WBC 1/μL, and RBC 1940/μL. HHV-6 IgG was 1:320 and IgM was negative prior to transplantation. The patient required intubation and blood pressure support. He was treated with IVIG weekly and Acyclovir initially. Multiplex RT-PCR analysis (Argene, Inc.) of the CSF was positive for HHV-6. The patient was started on ganciclovir when the data was obtained; however his status had improved prior to the change in medications. Follow-up HHV-6 titers 4 weeks after decompensation revealed HHV-6 IgG 1:1280. The patient developed grade 2–3 GVHD of the gut approximately day 55. Based on the MRI findings, the PCR positivity of the spinal fluid and the amnesia, we suspect that this is active HHV-6 infection. There have been several cases of encephalitis due to HHV-6 in HPC transplant patients who have presented with amnesia and who have temporal enhancement on MRI. HHV-6 can be a serious pathogen in HPC recipients receiving reduced-intensity preparative regimens.

The clinical syndrome of veno-occlusive disease (VOD) of the liver after hematopoeitic stem cell transplant (HSCT) is characterized by jaundice, painful hepatomegaly and fluid retention with weight gain. Cytoreductive chemotherapy is felt to be the primary cause of VOD, along with other risk factors. The incidence of VOD in adults undergoing HSCT ranges between 25% to 65%. VOD is considered to be the third leading cause of mortality (3% to 67%) after GVHD and infection in HSCT patients. The pathophysiology of VOD is not clear but the underlying mechanism is felt to be due to high dose chemotherapy causing endothelial injury of the sinusoids and small hepatic venules. This endothelial injury induces a local hypercoagulable state by activating the coagulation cascade and favoring clot formation. Fibrin related aggregates and entrapment of fluid and cellular debris occlude the small pores that perforate the endothelial lining. This causes hepatic venous outflow obstruction that generates a post sinusoidal intrahepatic portal hypertension which is responsible for the clinical features of VOD. Low dose heparin has been used as an anticoagulant in the prophylaxis of VOD. Ursodiol, a hydrophilic nonhepatotoxic bile salt, may be beneficial in VOD prevention as it may replace more toxic bile salts preventing damage by cholestasis. Glutathione (GSH), a biosynthetic derivative of glutamine, is depleted during chemotherapy. Supplemental glutamine has been shown to preserve GSH concentration thereby preventing hepatocellular damage seen in VOD. Based on this information, we conducted a retrospective study looking at 92 patients in our institution from January 2002 to present who were treated with low dose heparin infusion (100 units/kg/day), ursodiol (300 mg po bid), and glutamine (7.5 gms po bid). This regimen was started on the day of admission and discontinued prior to discharge. We reviewed the signs and symptoms of VOD using the Seattle criteria. Hepatic doppler was obtained to document reversal of flow in hepatic and portal venous circulation. The patient characteristics are shown in the table below. Out of 92 patients, 2 (2%) developed signs and symptoms consistent with VOD with negative color doppler studies. Both of the patients received allogeneic sibling transplants. Our experience demonstrates a relatively low incidence of VOD in HSCT patients with the above prophylactic regimen and we recommend its use.TablePatient CharacteristicsAgeMedian 48 yearsRange 22–66 yearsSex/(N) 92Male 57Female 35DiagnosisLeukemia/lymphoma 38/27Multiple myeloma/ solid tumors 25/2Type of transplantAutologous 77Allogeneic 15Conditioning regimenChemotherapy with total body irradiation 9Chemotherapy 83MDS, myelodysplastic syndrome. Open table in a new tab MDS, myelodysplastic syndrome.

Fungal infection is one of the most important causes of morbidity and mortality in hemopoeitic stem cell transplant (HSCT) recipients. The growing incidence of fungal infection is related to several factors including prolonged granulocytopenia, use of broad-spectrum antibiotics, conditioning regimens, and use of immunosuppression to avoid graft-versus-host disease. Amphotericin B with or without 5-flucytosine is considered the standard therapy for acute candidiasis with fluconazole as an alternative. Amphotericin B is also the first-line therapy for invasive aspergillosis in neutropenic patients. However nephrotoxicity is a major side effect of amphothericin B, particularly in patients with HSCT needing cyclosporine concurrently with amphotericin B. Both of these drugs are nephrotoxic and impaired renal function may be observed. Even with the development of the liposomal formulations of amphotericin B, there is still about a 20% risk of nephrotoxicity. Possible liposomal amphotericin B-induced nephrogenic diabetes insipidus has also been reported. Third generation triazoles have become available and have broadened the spectrum of effects against invasive aspergillosis. The efficacy of voriconazole (VRC) in the treatment of invasive aspergillosis in patients with acute myeloid leukemia undergoing HSCT has been reported. However there is no report regarding the adverse effects of VRC in the management of HSCT patients (PubMed Jan. 2001-Oct. 2003). Therefore we conducted this retrospective study to assess the adverse effects of VRC in HSCT patients (Jan. 2002 to Oct. 2003) and to evaluate the safety of the empiric use of VRC in HSCT patients. A total of 31 patients post HSCT received VRC. The characteristics of the patients are shown in table.1. All adverse events and laboratory abnormalities during treatment and follow-up were recorded and their relationship to VRC was determined. There were two patients with mild elevation in liver function tests not necessitating discontinuation of VRC with spontaneous normalization of liver function tests while on VRC. There was one patient with confusion, noted three days after the initiation of VRC while on narcotics. The confusion resolved upon discontinuing VRC and adjusting narcotics. VRC was not restarted due to resolution of fever and engraftment. Unlike prior reports we did not observe any skin rashes or visual disturbances. Our experience confirms the safety and tolerability of VRC in HSCT patients. TableNumber of patients31Mean age (range)48 (25–65)SexMale 24 (77%), Female 7 (23%)Underlying diseaseAML 11 (36%), NHL 7 (22%), HD 4 (13%), MM 4 (13%), ALL 3 (10%), CML 1 (3%), Germ cell 1 (3%)Type of HSCTAuto 28 (90%), Allo 3 (10%)Mean days of neutropeina (range)19 (7–57)Route of VRC administrationPO 15 (49%), IV 10 (32%), IV+PO 6 (19%)Dose of VRC400mg q12hr for two doses then 200mg q 12hrMean days of VRC administration (range)13 (2–45)Adverse effectsElevation of LFT's 2 (6%), Confusion 1 (3%)HSCT, hemopoietc stem cell transplant; VRC, voriconazole; AMI, acute myeloid leukemia; CML, chronic myeloid leukemia; ALL, acute lymphoid leukemia; MM, multiple myeloma; HD, Hodgkin's disease; NHL, non-Hodgkin's lymphoma; LFT, liver function test. Open table in a new tab HSCT, hemopoietc stem cell transplant; VRC, voriconazole; AMI, acute myeloid leukemia; CML, chronic myeloid leukemia; ALL, acute lymphoid leukemia; MM, multiple myeloma; HD, Hodgkin's disease; NHL, non-Hodgkin's lymphoma; LFT, liver function test.