Background:
Sickle cell disease (SCD) is a hemoglobinopathy that characteristically gives rise to a number of complications triggered by hemolytic anemia and vaso-occlusion. The prevalence of the ...disease is highest in sub-Saharan Africa, with the highest being in Nigeria where it affects over 6 million people.In spite of its overwhelming burden in Nigeria and the serious complications that result as a consequence, there is little in terms of epidemiological data specific to Nigeria regarding morbidity and management of the disease. Treatment of SCD and its complications includes early screening, patient education, genetic counseling, prophylaxis in the form of penicillin, vaccinations, folate supplementation, and the appropriate use of hydroxyurea (HU). While the efficacies of these treatments have been well documented in the West, morbidity and mortality due to SCD is still a significant public health problem in Nigeria. Particularly, HU has proved to be an effective disease-modifying treatment in the West. Many believe HU to be under-prescribed in Nigeria,but there is conflicting evidence. This study sought to assess the use of disease-modifying and preventive treatments, as well as barriers to treatment of sickle cell disease patients in Ibadan, Nigeria.
Methods:
We surveyed 50 outpatients at the University College Hospital of Ibadan (UCH) about their past and current treatment of SCD. Patients above age 12 with a primary diagnosis of SCD of any genotype were included. IRB approval was obtained through the UCH Ethics Committee and the Dartmouth College Committee for Protection of Human Subjects. All surveys were done on paper, and were administered to participants non-literate in English through a trained interpreter. Responses were input into SurveyMonkey and Excel for descriptive statistical analysis.
Results:
Of the people that submitted survey responses, 54% were male and 45% were female. The majority of respondents (84%) indicated that they had the SS genotype, while 14% were of SC genotype and 2% were uncertain of their genotype. The majority of respondents were between the ages of 19-45, and the majority had completed a university degree or higher education. When asked about prevention of SCD crises, 73% of respondents indicated they plan to seek genetic counseling prior to having children. Eighty-two percent of respondents indicated that they have taken prophylactic anti-malarials, while fewer people indicated that they use mosquito nets regularly for prevention of malaria (62%). Complication rates arising from SCD are listed in Table 1. When asked about pharmacotherapy options for treatment of SCD, 96% of respondents had been prescribed folate, compared to the 14% and 46% of respondents who had been prescribed oral penicillin and HU therapies, respectively. Compliance of the above drugs was relatively high as well, as the percentage of people who indicated they have taken folate (90%), penicillin (14%), and HU (42%) correlated similarly with those who had been prescribed. While the rate of those who had taken HU seem relatively high, the majority of those who had taken HU were doing so through the clinical trials of the drug being held at UCH (69%), rather than through an outside prescriber (31%). Of the 22 respondents not taking HU, 5 (23%) indicated that they would like to be taking it but are not able to, compared to the 7% of people not on penicillin who would like to be taking it. The largest potential barriers to treatment were inability to get to a hospital or clinic when necessary (16%) and lack of information about treatment options (32%).
Conclusions:
The most common treatment for SCD was folate therapy, followed by HU. Many patients receiving HU were formerly or currently enrolled in the clinical trials being run at UCH, which may suggest that it is not commonly prescribed by their regular providers. Most patients had faced at least one complication from SCD, and feel that their biggest deficits in treatment of SCD stem from their inability to get to a clinic or hospital in the event of a complication, and lack of information of the breadth of options that exist for management. More investigation remains to be done about the reasons for decreased usage of HU therapy among providers in Nigeria, and the efficacy of this treatment among adult patients. Given the low utilization of HU in this region, more follow up studies should be done about barriers such as cost, compliance, and access.
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Background: Patients often require critical management during chemotherapy and may need constant monitoring during and post-treatment in an inpatient (IP) unit. However, many ...patients can receive safe and effective administration of chemotherapy in an outpatient (OP) infusion setting, which respects patient’s wishes to shorten hospitalization stays. Optimizing OP treatment can also result in better utilization of resources that require critical monitoring. Since IP chemotherapy is not reimbursed separately, it is often considered a financial loss. This study evaluated the opportunity to decrease length of stay (LOS), reduce costs for our hematology/oncology inpatient practice, and increase utilization of a new infusion suite adjacent to IP unit. Methods: Work followed a Lean Six Sigma methodology – Define, Measure, Analyze, Improve, and Control. Multi-disciplinary clinical teams worked with quality improvement subject matter experts to explore regimens associated with inpatient administration of high-cost medications. Rituximab-based regimens were identified as the greatest opportunity to optimize cost reduction in the IP unit. The team set a goal to deliver rituximab as an OP in the infusion suite following hospital discharge. Baseline utilization of rituximab in the IP unit, revenue of the new infusion suite, and mean LOS for patients receiving R-EPOCH, a rituximab based regimen, were determined. Results: Percentage of IP rituximab administration was reduced by 56% resulting in $355,506 of cost avoidance in the IP unit. Mean quarterly revenue in the OP infusion suite increased from $104,363 at baseline to $293,607 through the first nine months by shifting rituximab to the OP setting, which projects to an annualized improvement of $756,976. Median LOS for patients receiving R-EPOCH was reduced by 12 hours (p < 0.001). Conclusions: Our intervention has resulted in decreased administration of high-cost chemotherapy in the IP unit, reduced LOS, and increased patient convenience. In addition, the significant revenue generated in the OP infusion suite will support improving patient services at our not-for-profit medical center.
Cutaneous T-cell lymphomas (CTCLs) are a rare group of mature T-cell lymphomas presenting primarily in the skin. The most common subtypes of CTCL are mycosis fungoides and its leukaemic variant ...Sézary’s syndrome. Patients with early-stage disease frequently have an indolent clinical course; however, those with advanced stages have a shortened survival. For the treating physician, the question of how to choose a particular therapy in the management of CTCL is important. These diseases span the disciplines of dermatology, medical oncology and radiation oncology. Other than an allo-geneic stem cell transplant, there are no curative therapies for this disease. Hence, many treatment modalities need to be offered to the patient over the course of their life. An accepted treatment approach has been to delay traditional chemotherapy, which can cause excessive toxicity without durable benefit. More conservative treatment strategies in the initial management of CTCL have led to the development of newer biological and targeted therapies. These therapies include biological immune enhancers such as interferon a and extracorporeal photopheresis that exert their effect by stimulating an immune response to the tumour cells. Retinoids such as bexarotene have been shown to be effective and well tolerated with predictable adverse effects. The fusion toxin denileukin diftitox targets the interleukin-2 receptor expressed on malignant T cells. Histone deacetylase inhibitors such as vorinostat and romidepsin (depsipeptide) may reverse the epigenetic states associated with cancer. Forodesine is a novel inhibitor of purine nucleoside phosphorylase and leads to apoptosis of malignant T cells. Pralatrexate is a novel targeted antifolate that targets the reduced folate carrier in cancer cells. Lastly, systemic chemotherapy including transplantation is used when rapid disease control is needed or if all other biological therapies have failed. As response rates to most of the biological agents used to treat CTCL are 25–30%, it is also reasonable to consider clinical trials with novel agents if one or two front-line therapies have failed, especially before considering chemotherapy. CTCL is largely an incurable disease with significant morbidity and more active agents are needed.
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Background: Living in a disadvantaged neighborhood may lead to survival disparities amongst patients with acute myeloid leukemia (AML). The Area Deprivation Index (ADI) is a measure of ...socioeconomic disadvantage by decile used to find discrepancies in healthcare outcomes. Increasing ADI negatively impacts ovarian cancer survival, with each decile increase in state or national ADI corresponding with a 9-10% greater risk of death (Hufnagel D et al., Cancer Epidemiology 2021). Higher ADI was correlated with decreased rates of adjuvant therapy for localized pancreatic cancer (Mora et al., American Journal of Surgery 2021). There are no American studies on ADI and AML. This study aims to identify the impact of socioeconomic disadvantage on survival outcomes for patients with AML in a rural population. Methods: A retrospective review of 180 adults with AML treated at Dartmouth Hitchcock Medical Center (DHMC) between 1/1/2010 - 12/31/2020. Patients with APML, primary treatment outside of DHMC, and those who opted for comfort measures only at diagnosis were excluded. Demographic data, including cytogenetics, treatment type, response to treatment, and survival at one year were recorded. Addresses from the medical record were used to determine state-level ADI using the University of Wisconsin Neighborhood Atlas. Results: Eighty-nine patients were included (64% male; 93% White). Median age was 65 years. Fifty-one patients (57%) had high risk disease, 31 intermediate risk (35%), 5 favorable risk (6%), and unknown risk for 2 (2%). Sixty-two patients (70%) received intensive chemotherapy 7+3 while 27 (30%) received less intensive therapy hypomethylating therapy. Twenty-six patients (29%) underwent transplantation. ADI decile was not associated with survival (p = 0.62). Furthermore, when ADI was divided into three groups (deciles 1-3, 4-6, 7-10) there was no difference in survival (p = 0.345). There was no effect of travel distance to DHMC median 81 minutes on OS (p = 0.619). There was a significant difference in survival outcomes between the two treatment types (p = 0.001), with median 25.7 vs. 7.1 months in the intensive vs. less intensive groups. This survival advantage was seen on multivariate analysis (p = 0.03). Females had better OS compared to males (p = 0.02) and older age was a negative predictor of outcome (p = 0.007). In those who achieved remission with induction, transplant led to improved survival (p = 0.04). Conclusions: There was no significant difference in treatment outcomes based on ADI, potentially due to equitable quality of care delivered regardless of socioeconomic disparities. This may be due to strong nurse navigation, social work support, specialists from the primary site who provide care in the community, and access to transplantation. Future studies to delineate the impact of various interventions for those with high ADI may be beneficial in treatment planning.
Background
The role of autologous stem cell transplantation (ASCT) in the first complete remission (CR1) of peripheral T‐cell lymphomas (PTCLs) is not well defined. This study analyzed the impact of ...ASCT on the clinical outcomes of patients with newly diagnosed PTCL in CR1.
Methods
Patients with newly diagnosed, histologically confirmed, aggressive PTCL were prospectively enrolled into the Comprehensive Oncology Measures for Peripheral T‐Cell Lymphoma Treatment (COMPLETE) study, and those in CR1 were included in this analysis.
Results
Two hundred thirteen patients with PTCL achieved CR1, and 119 patients with nodal PTCL, defined as anaplastic lymphoma kinase–negative anaplastic large cell lymphoma, angioimmunoblastic T‐cell lymphoma (AITL), or PTCL not otherwise specified, were identified. Eighty‐three patients did not undergo ASCT, whereas 36 underwent consolidative ASCT in CR1. At the median follow‐up of 2.8 years, the median overall survival was not reached for the entire cohort of patients who underwent ASCT, whereas it was 57.6 months for those not receiving ASCT (P = .06). ASCT was associated with superior survival for patients with advanced‐stage disease or intermediate‐to‐high International Prognostic Index scores. ASCT significantly improved overall and progression‐free survival for patients with AITL but not for patients with other PTCL subtypes. In a multivariable analysis, ASCT was independently associated with improved survival (hazard ratio, 0.37; 95% confidence interval, 0.15‐0.89).
Conclusions
This is the first large prospective cohort study directly comparing the survival outcomes of patients with nodal PTCL in CR1 with or without consolidative ASCT. ASCT may provide a benefit in specific clinical scenarios, but the broader applicability of this strategy should be determined in prospective, randomized trials. These results provide a platform for designing future studies of previously untreated PTCL.
This large prospective cohort study directly compares the survival outcomes of patients with nodal peripheral T‐cell lymphoma in first complete remission with or without consolidative autologous stem cell transplantation. Autologous stem cell transplantation is associated with superior survival for patients with advanced‐stage disease or an intermediate‐to‐high International Prognostic Index and with improved overall and progression‐free survival for patients with angioimmunoblastic T‐cell lymphoma.
So what is the consensus of when to use TSEBT? The NCCN guidelines recommend TSEBT at a dose of 30-36 Gy for patients with "severe skin symptoms or generalized thick plaque or tumor disease, or poor ...response to other therapies," and the guidelines also list the possibility of combining TSEBT with adjuvant therapies such as interferon or bexarotene (Targretin). 2 Other adjuvant treatments not mentioned in the guidelines include extracorporeal photopheresis and histone deacetylase inhibitors. The European Organisation for Research and Treatment of Cancer (EORTC) recommends TSEBT for stage IB and IIA (patch-plaque) MF. 6 For limited stage IIB (tumor) MF treated with TSEBT, the 5-year progressionfree survival approaches 50%. 6 For more extensive tumors, TSEBT is considered palliative, because the disease typically recurs. 6 For stage III (erythrodermic) MF or SS, patients without peripheral blood involvement can be treated with TSEBT as initial therapy with 66% 10-year progression-free survival, however, for those with peripheral blood involvement TSEBT is considered palliative. At the Dartmouth Hitchcock Medical Center (DHMC) multidisciplinary practice for cutaneous T-cell lymphomas, patients with tumors or thickly indurated plaques are often referred for photon beam radiation and then treated with systemic therapy such as bexarotene and/or interferon-alpha. For more extensive tumors, we do consider first-line TSEBT if immediate skin control is needed but follow this with systemic therapy because of the high relapse rate. The penetration of TSEBT is only to a depth of 4-5 mm, so for thicker plaques or more vertical tumors, TSEBT may not be sufficient unless "boosts" are given to discrete tumors. For erythrodermic MF without peripheral blood involvement, we consider TSEBT if immediate disease control is needed, and follow this with systemic therapy. At DHMC, as at other centers that offer TSEBT, many patients with MF travel more than 1 hour for consultation and treatment, which makes TSEBT less feasible for many. We consider extracorporeal photopheresis, PUVA, bexarotene, and interferon-alpha alone or in combination for erythrodermic MF. For erythrodermic SS, we prefer extracorporeal photopheresis in combination with bexarotene and/or interferon-alpha. TSEBT can be also used to palliate otherwise difficult to treat diffuse skin patches, tumors, or erythrodermic patients who are refractory to treatment with other agents, although more heavily pretreated patients are less likely to have a durable response.
Lipoprotein lipase (LPL) has emerged as a distinct prognostic marker for chronic lymphocytic leukemia (CLL), a heterogeneous disease with a similar heterogeneity in life expectancy. While many prior ...studies have focused on tumor expression of LPL mRNA, LPL surface protein expression has been less robustly studied as a prognostic marker. A novel antibody developed at Geisel School of Medicine at Dartmouth has been previously utilized in immunohistochemistry assays of breast and prostate cancer. With this study we aimed to use this antibody as a flow cytometry marker of surface LPL expression correlated with overall survival and time to first treatment. Of the 19 patients studied, our data show that LPL surface protein expression as measured by flow cytometry trended toward a protective effect on overall survival and overall better prognosis.
Introduction: The real-world outcomes in patients (pts) with PCALCL in the era of targeted therapies like Brentuximab Vedotin (BV) is not well defined due to lack of large multicenter studies. We ...conducted a multicenter retrospective RWA to assess patient and disease characteristics, treatment patterns, survival outcomes and impact of novel therapies in this rare type of cutaneous T cell lymphoma (CTCL). Methods: A total of 95 adult (≥18 years) pts from 8 academic institutions in the United States diagnosed from 2010-2022 were included in the analysis. The study was approved by the Institutional Review Boards at the respective sites. Demographic and disease factors were summarized by descriptive statistics. Overall survival (OS) was estimated by Kaplan-Meier method and compared using log rank method. Results: In our cohort, the median age at diagnosis was 63 (range 18-93) years. The majority of pts were male 60%, white 79%, and had good performance status (PS) ECOG 0-1 (93%). Median time from initial presentation to diagnosis was 1.8 (range 0-211) months. Most common initial skin presentation was tumor 46% (44/95), followed by plaques 27% (26/95) and patches 15% (14/95). No pt presented with erythroderma. Median size of the largest lesion was 2 (range 0.5-20) cm. 63% had early stage (IA-IIA) disease and 86% had <5 skin lesions at the time of initial diagnosis. Furthermore, palpable lymph node (LN) (10%) and elevated LDH (18%) were uncommon at diagnosis. Initial treatments include localized radiation 60%, surgical excision 21% and topical steroids 11%. A small subset of pts received systemic treatments like CHOP 13% (12/95), BV 8% (8/95) and oral methotrexate 7% (7/95) as frontline therapy. A proportion of pts received XRT with CHOP (6/12) and BV (2/8). The overall response rate (ORR) to initial therapy was 68% (65/95) with 61% achieving a CR and 17% had primary refractory disease (stable and progressive disease). Relapse rate after 1st line therapy was 52% (49/95). In our cohort a total of 22 pts received BV after frontline therapy, of which 19 were BV naïve and 3 were re-treated. At the time of last follow up, 27% of our cohort were still on treatment, 78% were alive and 21% were dead; only 3% of deaths were attributed to the lymphoma. The median OS was 128 months (95% CI: 78.4-NA) (Figure 1) with a median follow up of 42 (range 0.5-123.5) months. The 5-year OS was 77%. On univariate analysis, older age (≥65 vs <65 years) (median OS 78 vs 128 months; p=0.004) and higher number of lesions (5-10 vs <5) (mOS 34 vs 128 months; p=<0.0001) were significant associated with OS (Table 1). Type and size of the skin lesions, presence of palpable LN, elevated LDH, stage, and treatment modalities had no impact on OS. Results of multivariate analysis will be presented at the conference. Conclusion: In this large multicenter RWA of PCALCL, excellent long-term survival was observed following frontline therapies that were mostly skin directed. The use of systemic therapies including BV were infrequent even in relapsed disease. Older age and increased number of skin lesions were associated with poor OS.
Purpose Patients with double-hit lymphoma (DHL) rarely achieve long-term survival following disease relapse. Some patients with DHL undergo consolidative autologous stem-cell transplantation ...(autoSCT) to reduce the risk of relapse, although the benefit of this treatment strategy is unclear. Methods Patients with DHL who achieved first complete remission following completion of front-line therapy with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or intensive front-line therapy, and deemed fit for autoSCT, were included. A landmark analysis was performed, with time zero defined as 3 months after completion of front-line therapy. Patients who experienced relapse before or who were not followed until that time were excluded. Results Relapse-free survival (RFS) and overall survival (OS) rates at 3 years were 80% and 87%, respectively, for all patients (n = 159). Three-year RFS and OS rates did not differ significantly for autoSCT (n = 62) versus non-autoSCT patients (n = 97), but 3-year RFS was inferior in patients who received R-CHOP compared with intensive therapy (56% v 88%; P = .002). Three-year RFS and OS did not differ significantly for patients in the R-CHOP or intensive therapy cohorts when analyzed by receipt of autoSCT. The median OS following relapse was 8.6 months. Conclusion In the largest reported series, to our knowledge, of patients with DHL to achieve first complete remission, consolidative autoSCT was not associated with improved 3-year RFS or OS. In addition, patients treated with R-CHOP experienced inferior 3-year RFS compared with those who received intensive front-line therapy. When considered in conjunction with reports of patients with newly diagnosed DHL, which demonstrate lower rates of disease response to R-CHOP compared with intensive front-line therapy, our findings further support the use of intensive front-line therapy for this patient population.
Recent publications have documented an increased prevalence of cutaneous T‐cell lymphoma (CTCL) in patients undergoing tumor necrosis factor alpha (TNF‐α) inhibitor therapy. Herein, we present an ...uncommon manifestation of mycosis fungoides (MF) with unique pathological findings after the initiation of adalimumab therapy for the treatment of psoriasis. One year after starting treatment, the patient noticed a slowly growing, eroded plaque on the left cheek, the biopsy of which demonstrated mixed granulomatous and adnexotropic lymphocytic infiltrate with features characteristics of MF. In the following months, the patient developed pink‐ and violet‐colored scaly plaques on the right posterior upper arm and right medial upper arm. Biopsy of these plaques also revealed findings compatible with MF. T‐cell receptor (TCR) clonality studies by PCR revealed identical T‐cell clones in the samples obtained from the cheek, right posterior upper arm, and right medial upper arm. TCR clonality studies of a long‐standing psoriatic plaque on the right thigh failed to reveal similar T‐cell clones. Blurring of histopathologic presentation by TNF‐α inhibitors could greatly complicate the identification of MF subtypes. Providers treating patients with TNF‐α inhibitors must be aware of the risk of cutaneous lymphoma development and the potential deviations from their expected presentations. In patients without an initial biopsy, the possibility of pre‐existing CTCL with psoriasiform presentation should be considered.
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