Referral Patterns and Clinical Outcomes for Transplant-Eligible Lymphoma and Myeloma Patients Evaluated at an Urban County Hospital.

Disparities in clinical care have been described for patients with limited insurance coverage or social support. We hypothesized that patients with relapsed Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), or multiple myeloma (MM) treated at an urban county hospital serving indigent and under-insured patients would face barriers for referral to a private academic transplant center for autologous stem cell transplantation (ASCT). Charts of patients with HL, NHL, or MM treated at Grady Memorial Hospital between 2007 and 2013 were reviewed, and 215 patients with diagnosis of HD (n=40), NHL (n=96), and MM (n=79). 55 patients were referred for ASCT consults and 160 patients were not referred. Reasons for transplant non-referral included established clinical criteria (64% of cases), poor performance status (13%), refusal (4%), moved/lost-to-follow-up (4%), medical non-compliance (3%), death (3%), or referral to another hospital (1%). Non-referral based upon socio-economic criteria included: lack of legal immigration status/insurance (2%), and lack of social support/substance abuse (2%). Among the 55 referred patients, 27 patients (49%) underwent ASCT. Median follow-up for all referred patients from the time of diagnosis was 3.9 [0.7-22.7] years. 5-year survival from the date of diagnosis for patients who received ASCT was 80.2% versus 65.7% for non-transplanted patients (log-rank test, p-value=0.11). While the referral process did not demonstrate significant barriers based upon insurance or social status, further evaluation is needed to identify modifiable factors that can improve referral and assess the impact of the Affordable Care Act on access to ASCT.

Pharmacoeconomic analysis of palifermin to prevent mucositis among patients undergoing autologous hematopoietic stem cell transplantation.

Trials have shown benefits of palifermin in reducing the incidence and severity of oral mucositis in patients with hematological malignancies undergoing autologous hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI)-based conditioning regimens. Similar outcome data are lacking for patients receiving non-TBI-based regimens. We performed a retrospective evaluation on the pharmacoeconomic benefit of palifermin in the setting of non-TBI-based conditioning and autologous HSCT. Between January 2002 and December 2010, 524 patients undergoing autologous HSCT for myeloma (melphalan 200 mg/m²) and lymphoma (high-dose busulfan, cyclophosphamide, and etoposide) as preparative regimen were analyzed. Use of patient-controlled analgesia (PCA) was significantly lower in the palifermin-treated groups (myeloma: 13% versus 53%, P < .001; lymphoma: 46% versus 68%, P < .001). Median total transplant charges were significantly higher in the palifermin-treated group, after controlling for inflation (myeloma: $167,820 versus $143,200, P < .001; lymphoma: $168,570 versus $148,590, P < .001). Palifermin treatment was not associated with a difference in days to neutrophil engraftment, length of stay, and overall survival and was associated with an additional cost of $5.5K (myeloma) and $14K (lymphoma) per day of PCA avoided. Future studies are suggested to evaluate the cost-effectiveness of palifermin compared with other symptomatic treatments to reduce transplant toxicity using validated measures for pain and quality of life.

Cost-effectiveness of posaconazole versus fluconazole for prevention of invasive fungal infections in U.S. patients with graft-versus-host disease.

PURPOSE: The results of a pharmacoeconomic study of the cost-effectiveness of posaconazole versus fluconazole in preventing invasive fungal infections (IFIs) in patients with graft-versus-host disease (GVHD) are reported. METHODS: The results of a randomized clinical trial suggested that posaconazole may be as effective as fluconazole for the prevention of IFIs in recipients of allogeneic cell transplants who develop severe GVHD and that posaconazole may be superior to fluconazole in reducing IFI-related deaths. Using published data from that trial and data from secondary sources, an economic model was developed to estimate the costs, IFIs avoided, and life-years saved with posaconazole versus fluconazole therapy. The results of the modeled 112-day treatment simulation were extrapolated to a lifetime horizon. RESULTS: In the modeled simulation, posaconazole therapy was associated with a lower probability of IFI development (0.05 versus 0.09), increased discounted life-years (7.87 life-years versus 7.66 life-years), and higher discounted costs per patient ($8,860 versus $5,710 in 2006 U.S. dollars) relative to fluconazole therapy. The estimated incremental cost-effectiveness of posaconazole versus fluconazole for IFI prophylaxis was $85,300 per IFI avoided and $15,300 per life-year saved. A sensitivity analysis indicated a 90% probability that the use of posaconazole for this purpose would be cost-effective at a threshold of $50,000 per life-year saved. CONCLUSION: Posaconazole is in the range of currently accepted criteria for cost- effectiveness relative to fluconazole for the prevention of IFIs among patients with GVHD.

Effectiveness and cost analysis of "just-in-time" salvage plerixafor administration in autologous transplant patients with poor stem cell mobilization kinetics.

BACKGROUND: Plerixafor is a recently Food and Drug Administration (FDA)-approved CXCR4 antagonist, which is combined with granulocyte-colony-stimulating factor (G-CSF) to facilitate stem cell mobilization of lymphoma and myeloma patients. STUDY DESIGN AND METHODS: To evaluate the effectiveness and the related costs of a "just-in-time" strategy of plerixafor administration, we performed a retrospective cohort study comparing 148 consecutive lymphoma and myeloma patients in whom mobilization was attempted during 2008 before the Food and Drug Administration (FDA) approval of plerixafor with 188 consecutive patients mobilized during 2009 after FDA approval. RESULTS: Plerixafor was administered to 64 of 188 patients considered to be at risk for mobilization failure due to either their medical history ("high risk," n = 23) or the occurrence of peripheral blood CD34+ count of fewer than 15 × 10(6) cells/L with a white blood cell count of greater than 10 × 10(9) cells/L after at least 5 days of G-CSF administration (just-in-time, n = 41). The success rates of collecting a minimum transplant CD34+ cell dose (≥2 × 10(6) cells/kg) or target cell dose (≥5 × 10(6) lymphoma or ≥10 × 10(6) CD34+ cells/kg myeloma) in the just-in-time patients compared favorably with the 36 poor mobilizers collected with G-CSF alone: 93% versus 72% and 42% versus 22%, respectively. CONCLUSIONS: The use of plerixafor in selected high-risk patients and poor mobilizers did not increase the total charges associated with stem cell collection when compared with poor mobilizers treated with G-CSF alone. The targeted use of plerixafor increased the overall success rate of mobilizing a minimum number of CD34+ cells from 93% to 98% in patients with hematologic malignancies scheduled for autotransplant and increased the overall charges associated with stem cell collection in all patients by an average of 17%.

Peripheral blood monitoring of chronic myeloid leukemia during treatment with imatinib, second-line agents, and beyond.

BACKGROUND: The current study was conducted to compare simultaneously obtained bone marrow (BM) cytogenetics (CTG), peripheral blood (PB) and BM fluorescence in situ hybridization (FISH), and quantitative real-time polymerase chain reaction (Q-PCR) for BCR-ABL1 in monitoring response to treatment with tyrosine kinase inhibitors and homoharringtonine (HHT) in patients with chronic myeloid leukemia (CML). METHODS: PB and BM FISH (n = 112 samples) and/or Q-PCR (n = 132 samples) for BCR-ABL1 were simultaneously obtained in 70 patients with Philadelphia chromosome-positive (Ph+) CML in chronic (68%), accelerated (16%), and blast phase (16%) before the initiation of therapy and during the course of treatment with imatinib (IM) (n = 40 patients), dasatinib (n = 20 patients), nilotinib (n = 4 patients), bosutinib (n = 18 patients), or HHT (n = 4 patients) for patients with newly diagnosed (n = 13 patients), IM-sensitive (n = 34 patients), IM-resistant (n = 30 patients), or IM-intolerant (n = 9 patients) disease. Eighteen patients were found to have Ph+ variants or karyotypic abnormalities in addition to the Ph+. RESULTS: Excellent correlations (r) were observed between PB and BM FISH (r = 0.95) and PB and BM Q-PCR (r = 0.87), as well as BM CTG and PB FISH (r = 0.89) and PB Q-PCR (r = 0.82). This correlation was not affected by the presence of the Ph+ variant or additional chromosomal abnormalities, the presence of ABL1 kinase domain mutations, phase of the disease, or treatment. CONCLUSIONS: PB FISH and Q-PCR appear to be reliable methods with which to monitor response to modern therapy in patients with all phases of CML.

The economic costs to United States hospitals of invasive fungal infections in transplant patients.

BACKGROUND: Patients with a solid organ transplant (SOTs) and hematopoietic stem cell or bone marrow transplants (HSC/BMTs) are at risk of contracting invasive fungal infections (IFIs). Data on the economic burden of IFIs in the United States are sparse. METHODS: We conducted a retrospective matched cohort study using the 2004-2005 Healthcare Cost and Utilization Project Nationwide Inpatient Sample. The IFI cohort included patients with ICD-9-CM codes indicating a transplant procedure and an IFI. Matched controls (transplant recipients without an IFI) were chosen based on age (10 year categories), sex, region, hospital type, year, and transplant type. Mortality, length of stay, and costs were reported overall, by transplant type, and by type of mycosis. RESULTS: Nine thousand eight hundred ninety-six patients underwent SOT, and 4661 underwent HSC/BMT. Of these, 80 (0.8%) SOT and 111 (2.4%) HSC/BMT patients had an IFI. Mean age was 41.8 years (SOT) and 37.8 years (HSC/BMT). Aspergillosis was the most common infection. Patients with an IFI had a 5-fold increase in mortality, an additional 19.2 hospital days, and $55,400 in excess costs compared with patients without an IFI. Excess mortality, length of stay, and costs varied by type of transplant and mycosis. CONCLUSION: The clinical and economic burden of IFIs in transplant recipients may be high.

Mortality, length of hospitalization, and costs associated with invasive fungal infections in high-risk patients.

PURPOSE: The mortality, length of hospitalization, and costs associated with invasive fungal infections (IFIs) in hospitalized patients were studied. METHODS: This retrospective database study used data from the 2004 Healthcare Cost and Utilization Project Nationwide In-patient Sample. Patients were selected for inclusion based on diagnostic codes corresponding to an IFI. A control group was matched to the IFI group based on high-risk conditions (i.e., cancer, infection with human immunodeficiency virus, chronic obstructive pulmonary disease, diabetes mellitus, and solid-organ, hematopoietic stem cell, or bone marrow transplant), age, sex, and hospital region and teaching status. Excess mortality, length of hospital stay, and costs were estimated as the differences between the IFI and control groups. RESULTS: A total of 11,881 patients were identified with a discharge diagnosis of an IFI who could be matched to a control. Frequent infections included candidiasis (40.2%), other mycoses (36.3%), and aspergillosis (16.4%). Patients with IFIs had a significantly higher mortality rate (15% versus 5%), mean +/- S.E. length of stay (18.7 +/- 0.4 days versus 7.3 +/- 0.1 days), and mean +/- S.E. costs ($44,726 +/- $1,255 versus $15,445 +/- $404) (p < 0.001 for all comparisons) than did patients without IFIs. The burden of IFIs varied by high-risk condition (highest for transplant recipients and patients with cancer) and type of infection (highest for candidiasis, zygomycosis, and aspergillosis). CONCLUSION: Examination of a large database showed that, compared with high-risk patients without IFIs, those with IFIs had higher mortality, a longer hospital stay, and higher costs associated with their hospitalization.

Cost-effectiveness of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infections among neutropenic patients in the United States.

OBJECTIVES: Clinical trial data indicate that posaconazole is superior to fluconazole (FLU) or itraconazole (ITRA) in preventing invasive fungal infections (IFIs) among neutropenic patients. Our objective was to assess the cost-effectiveness of posaconazole versus FLU or ITRA for prevention of IFIs among neutropenic patients. METHODS: We used modeling techniques to assess the cost-effectiveness of posaconazole versus FLU or ITRA in the prevention of IFIs among patients with acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS) and chemotherapy-induced neutropenia. The probabilities of experiencing an IFI, IFI-related death, and death from other causes over 100 days of follow-up were estimated from clinical trial data. Long-term mortality, drug costs, and IFI treatment costs were obtained from secondary sources. RESULTS: Posaconazole is associated with fewer IFIs per patient (0.05 vs. 0.11) relative to FLU or ITRA over 100 days of follow-up, and lower discounted costs ($3900 vs. $4500) and increased life-years (2.50 vs. 2.43 discounted) over a lifetime horizon. Results from a probabilistic sensitivity analysis indicate that there is a 73% probability that posaconazole is cost saving versus FLU or ITRA and a 96% probability that the incremental cost-effectiveness ratio for posaconazole is at or below $50,000 per life-year saved. CONCLUSIONS: We conclude that posaconazole is very likely to be a cost-effective alternative to FLU or ITRA in the prevention of IFIs among neutropenic patients with AML and MDS, and may result in cost savings.