Rachel B Salit

Fred Hutchinson Cancer Research Center, Seattle, Washington, United States

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Publications (17)127.61 Total impact

  • Rachel B Salit · Filippo Milano · Colleen Delaney
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    ABSTRACT: For patients with disease relapse or graft failure after allogeneic hematopoietic cell transplant (HCT), there are few treatment options and survival rates are exceedingly low. Due to the unacceptably high risk of transplant related mortality, second allogeneic HCTs are often not considered. Herein, we report the outcomes of 23 patients median age 33 years undergoing a second allogeneic transplant with unrelated cord blood donor grafts between 2006-2013. Indications for second HCT were relapse (n = 19), graft failure (n = 3) and donor derived MDS (n = 1). 10 patients received reduced intensity conditioning (RIC), and 13 patients received either myeloablative (MAC) or middle intensity (MIDI) conditioning. Twenty patients received a double cord blood transplant (CBT). All patients engrafted at a median of 22 days (range day 6 - 49). Death prior to day 100 occurred in 5 patients. Overall disease free survival (DFS), treatment related mortality (TRM), and relapse at 2 years were 31%, 33%, and 35% respectively. Two-year DFS in the 13 patients receiving MAC or MIDI conditioning was slightly higher at 46%. Our results demonstrate that second allogeneic HCT using cord blood as the graft source should be considered in patients who have relapsed or experience graft failure following an allogeneic HCT.
    No preview · Article · Oct 2015 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
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    ABSTRACT: Background: Low patient-reported resilience is associated with an ongoing risk of poor health and psychosocial outcomes. Using a large cross-sectional sample of survivors of hematopoietic cell transplantation (HCT), this study explored associations between patient-reported resilience, psychological distress, posttraumatic growth, and health-related quality of life. Methods: Between July 1, 2013 and June 30, 2014, the annual Fred Hutchinson Cancer Research Center (FHCRC) posttransplant survivorship survey queried patient-reported health and functional status and included instruments assessing psychosocial outcomes: the 10-item Connor-Davidson Resilience Scale, the Posttraumatic Growth Inventory, the Cancer and Treatment Distress measure, and the 12-item Medical Outcomes Study Short Form quality-of-life scale. Multivariate linear and logistic regression models included demographic and health covariates extracted from the FHCRC research database. Results: Among 4643 adult survivors of HCT, 1823 (39%) responded after a single mailing and subsequent reminder letter. The participants' median age was 59 years (interquartile range [IQR], 50-66 years); 52.5% were male, and most were non-Hispanic white. The median time since HCT was 9 years (IQR, 3-18 years). Lower patient-reported resilience was associated with chronic graft-versus-host disease of higher severity, lower performance scores, missing work because of health, and permanent disability (all P < .0001). After adjustments for demographic and health characteristics, patients reporting low resilience scores had higher odds of having psychological distress (odds ratio [OR], 3.0; 95% confidence interval [CI], 2.1-4.3) and being in the lowest quartile for mental health-related quality of life (OR, 5.9; 95% CI, 4.4-8.0). Conclusions: Patient-reported resilience is independently associated with health and psychosocial outcomes. Future studies must determine whether interventions can bolster resilience and improve survivorship outcomes. Cancer 2015;121:4250-4257. © 2015 American Cancer Society.
    No preview · Article · Aug 2015 · Cancer

  • No preview · Article · Feb 2015 · Biology of Blood and Marrow Transplantation
  • Rachel B. Salit · H. Joachim Deeg
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    ABSTRACT: Myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell disorders. While some MPN patients have an indolent course, all are at risk of progressing to severe marrow failure or transforming into acute leukemia. Allogeneic hematopoietic cell transplantation (allo-HCT) is the only potential curative therapy. Major pre-transplant risk factors are disease stage of the MPN, the presence of comorbid conditions and the use of HLA non-identical donors. The development of reduced-intensity conditioning regimens has allowed for successful allo-HCT even for older patients and patients with comorbid conditions. The pre-transplant use of JAK2 inhibitors, which may be effective in down staging a patient's disease, may improve the outcomes following allo-HCT. Published by Elsevier Inc.
    No preview · Article · Dec 2014 · Hematology/Oncology Clinics of North America
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    ABSTRACT: The mortality rate of alveolar hemorrhage following allogeneic hematopoietic stem cell transplantation is greater than 60% with supportive care and high dose steroids. We performed a retrospective cohort analysis to assess the benefits and risks of rFVIIa as a therapeutic adjunct for alveolar hemorrhage. From 2005 to 2012, 57 episodes of alveolar hemorrhage occurred in 37 patients. Fourteen episodes (in 14 patients) were treated with steroids alone and 43 episodes (in 23 patients) were treated with steroids and rFVIIa. The median (interquartile range) steroid dose was 1.9 mg/kg/d (0.8 - 3.5; methylprednisolone equivalents) and did not differ statistically between the two groups. The median rFVIIa dose was 41 μg/kg (39-62) and a median of 3 doses (2-17) was administered per episode. Concurrent infection was diagnosed in 65% of the episodes. Patients had moderately severe hypoxia (median PaO2/FiO2, 193 [141-262]); 72% required mechanical ventilation and 42% survived to extubation. The addition of rFVIIa did not alter time to resolution of alveolar hemorrhage (p = 0.50), duration of mechanical ventilation (p = 0.89), duration of oxygen supplementation (p = 0.55), or hospital mortality (p = 0.27). Four possible thrombotic events (9% of 43 episodes) occurred with rFVIIa. rFVIIa when used in combination with corticosteroids did not confer clear clinical advantages compared to corticosteroids alone. In patients with AH following hematopoietic stem cell transplant, clinical factors (i.e. worsening infection, multiple organ failure or recrudescence of primary disease) may be more important than the benefit of enhanced hemostasis from rFVIIa.
    Full-text · Article · Mar 2014 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
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    ABSTRACT: Reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (RIC-alloHSCT) is associated with lower toxicity but higher rates of prolonged mixed chimerism than myeloablative conditioning. Decreased pre-transplant host T-cell numbers are associated with less graft rejection and early full donor chimerism. To compensate for variability in pre-transplant host lymphocyte numbers and facilitate the achievement of rapid full donor chimerism, we tested a strategy of targeted lymphocyte depletion (TLD) using chemotherapy at conventional doses to provide cytoreduction and lymphocyte depletion prior to RIC-alloHSCT. 111 patients with advanced hematologic malignancies received 1-3 cycles of conventional-dose chemotherapy to reduce circulating lymphocytes to a predetermined level. Patients then underwent RIC-alloHSCT from HLA-matched siblings. Patients received a median of 2 cycles of TLD chemotherapy resulting in a median 71% decline in CD4+ count. All patients engrafted; there were no late graft failures. By Day +14, median CD3+ chimerism was 99% donor and was significantly associated with lower post-TLD CD4+ counts (p = 0.012). One and 5-year treatment-related mortality was 15% and 21%, respectively. At one-year follow-up, 66% of patients had achieved complete remission (CR) of which 92% were not in CR at the time of transplant. Overall survival at one and five years post-transplant was 66% and 47%, respectively.
    Preview · Article · Aug 2013 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
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    Preview · Article · Feb 2013 · Biology of Blood and Marrow Transplantation
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    ABSTRACT: Aim The goal of the study was to evaluate a correlation of an HLA restricted minor histocompatibility antigen (mHAg) with the development of graft versus host disease (GVHD). The objective was to assess whether testing for mHAgs should be done on a prospective basis, to guide donor selection and reduce the high incidence of GVHD in post-transplant allografts when treating hematologic malignancies. Methods A cohort of 45 patient/unrelated donor pairs, 10/10 HLA match, in the NCI protocol 07-C-0195 were typed for 18 mHAgs using an SSP-PCR typing kit (Minor Histocompatibility Antigen Typing Kit; Life Technologies, Carlsbad, CA). GVHD data was obtained from the clinical protocol database. Patients were determined not evaluable if they relapsed or had residual disease requiring a donor lymphocyte infusion or additional chemotherapy. Due to clinical status, one patient could not be evaluated for acute or chronic GVHD. In addition, 4 patients could not be evaluated for chronic GVHD. Therefore, 44 out of 45 patients were evaluated for acute GVHD and 40 out of 45 patients for chronic GVHD. Statistical analysis was performed using the Fisher exact test. Results Patients with mHAg mismatches were analyzed for both acute and chronic GVHD. Preliminary analysis demonstrates that out of the 45 patient/donor pairs, 30 pairs had mHAgs mismatched in the GVHD direction. 19 of the 30 patients (63%) with mismatches developed acute GVHD (P = 0.062) and 15 of the 30 patients (50%) with mismatches developed chronic GVHD (P = 0.061). Nine of these patients developed both acute and chronic GVHD. Conclusions Data suggests some correlation regarding mHAg mismatches and the development of GVHD. Further study and a larger cohort may allow a gauge for the efficacy of testing for the mHAgs on a prospective basis. Testing on a prospective basis could give clinicians more knowledge to select donors with a favorable mHAg constellation to reduce the risk of their transplant patients developing GVHD.
    No preview · Article · Oct 2012 · Human Immunology

  • No preview · Article · Oct 2012 · Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology
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    ABSTRACT: There is currently no standard chemotherapy regimen for patients with lymphoid malignancies being considered for reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation (RIC-alloHSCT). The ideal regimen would provide disease control and result in lymphocyte depletion to facilitate engraftment. To this end, we developed a novel regimen by adding fludarabine to dose-adjusted continuous-infusion etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus with or without rituximab (DA-EPOCH-F/R). One hundred forty-seven patients with lymphoid malignancy (median age, 50 years) who had heavily pretreated (median prior regimens, three) and chemo-refractory (47%) disease were treated with DA-EPOCH-F/R before RIC-alloHSCT. Patients received one to three consecutive cycles until achieving lymphocyte depletion (CD4(+) count < 200/μL) or progressive disease. Overall response rate was 41%; 39% of patients had stable disease. Toxicity included grade 4 neutropenia in 65% and thrombocytopenia in 25% of patients. DA-EPOCH-F/R resulted in lymphocyte depletion (P < .001), which was inversely associated with serum interleukin (IL) 7 and IL-15 levels. Of 147 patients, 143 patients proceeded to RIC-alloHSCT. Patients with lower CD3(+) (P < .001), CD4(+) (P < .001), and CD8(+) (P < .001) T-cell counts after DA-EPOCH-F/R were more likely to achieve full donor lymphoid chimerism by day +14 after transplant. Relative to nonresponders to DA-EPOCH-F/R, patients with complete and partial response had increased event-free survival (77.4 v 4.8 months; P < .001) and overall survival (98.5 v 16.2 months; P < .001). DA-EPOCH-F/R safely provides tumor cytoreduction and lymphocyte depletion, thereby offering a bridge to RIC-alloHSCT in patients with aggressive lymphoid malignancies.
    Preview · Article · Feb 2012 · Journal of Clinical Oncology
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    ABSTRACT: Chronic graft-versus-host disease (cGVHD) remains a major cause of non-relapse morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Currently there are no accepted measures of cGVHD activity to aid in clinical management and disease staging. We analyzed clinical markers of inflammation in the sera of patients with established cGVHD and correlated those with definitions of disease activity. In all, 189 adults with cGVHD (33% moderate and 66% severe according to National Institutes of Health (NIH) global scoring) were consecutively enrolled onto a cross-sectional prospective cGVHD natural history study. At the time of evaluation, 80% were receiving systemic immunosuppression and failed a median of four prior systemic therapies (PST) for their cGVHD. Lower albumin (P<0.0001), higher C-reactive protein (P = 0.043), higher platelets (P = 0.030) and higher number of PST (P<0.0001) were associated with active disease defined as clinician's intention to intensify or alter systemic therapy due to the lack of response. Higher platelet count (P = 0.021) and higher number of PST (P<0.0001) were associated with more severe diseased defined by NIH global score. This study identified common laboratory indicators of inflammation that can serve as markers of cGVHD activity and severity.
    Full-text · Article · Oct 2011 · Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
  • Jason M Elinoff · Rachel B Salit · Hans C Ackerman

    No preview · Article · Aug 2011 · New England Journal of Medicine
  • Rachel B Salit · Michael R Bishop
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    ABSTRACT: Reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) can result in reliable donor engraftment, relatively low treatment-related mortality, and sustained remissions in the treatment of multiple myeloma. However, substantial cytoreduction pre-allografting is often necessary because of a variable graft-versus-myeloma effect. The use of RIC allogeneic HSCT immediately after autologous HSCT provides a temporal separation between tumor reduction by high-dose chemotherapy and the graft-versus-myeloma effect. There are currently a number of prospective trials attempting to address the issue of whether this strategy leads to decreases in relapse and/or improvement in overall survival as compared with double autologous transplants. Unfortunately, similar to autografting, relapse remains the major cause of treatment failure after RIC allogeneic HSCT. To improve treatment results with allografting, consideration should be given to incorporating immunomodulatory drugs and targeted treatments to enhance pretransplantation remission status, as posttransplantation maintenance therapy, or in combination with donor lymphocyte infusions for refractory or relapsed disease. Studies exploring these strategies are ongoing.
    No preview · Article · Jun 2011 · Clinical lymphoma, myeloma & leukemia
  • Rachel B Salit · Michael R Bishop

    No preview · Article · Apr 2011 · Oncology (Williston Park, N.Y.)
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    Preview · Article · Feb 2011 · Biology of Blood and Marrow Transplantation
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    ABSTRACT: We describe a case of invasive fungal infection caused by Volvariella volvacea following double umbilical cord blood transplantation (UCBT). Although infections caused by several mushroom species have been documented, we believe this to be the first published report of invasive infection with Volvariella volvacea, an edible mushroom belonging to Agaricales.
    Preview · Article · Nov 2010 · Journal of clinical microbiology
  • Rachel B Salit · Michael R Bishop · Steven Z Pavletic
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    ABSTRACT: Although the majority of patients with Hodgkin lymphoma achieve sustained remission with frontline treatment, there is still a subset of patients with much less favorable prognosis. The current standard of care for Hodgkin lymphoma patients with relapsed or refractory disease is autologous stem cell transplantation. However, no randomized trial has compared autologous stem cell transplantation with allogeneic stem cell transplantation prospectively, and most studies comparing allogeneic stem cell transplantation with historical controls of autologous stem cell transplantation use a myeloablative conditioning reference group. With the more frequent use of reduced-intensity conditioning transplantation in recent studies, the role for allogeneic stem cell transplantation in Hodgkin lymphoma patients is being redefined. In contrast to other types of lymphomas, Hodgkin lymphoma patients are younger at diagnosis, which makes a curative strategy such as allogeneic stem cell transplantation particularly appealing. This review examines the role of allogeneic stem cell transplantation in Hodgkin lymphoma by looking at both retrospective and prospective analyses in the era of reduced-intensity conditioning transplantation, donor lymphocyte infusions, and biologically based treatments.
    No preview · Article · Oct 2010 · Current Hematologic Malignancy Reports

Publication Stats

90 Citations
127.61 Total Impact Points

Institutions

  • 2013-2015
    • Fred Hutchinson Cancer Research Center
      • Division of Clinical Research
      Seattle, Washington, United States
    • University of Washington Seattle
      Seattle, Washington, United States
  • 2011-2014
    • National Cancer Institute (USA)
      • • Experimental Transplantation and Immunology Branch
      • • Center for Cancer Research
      Maryland, United States
  • 2010-2012
    • National Institutes of Health
      • • Branch of Experimental Transplantation and Immunology
      • • Branch of Medical Oncology Branch and Affiliates
      Maryland, United States
    • NCI-Frederick
      Фредерик, Maryland, United States