Publications by authors named "Andrew S Artz"

75 Publications

Characterize, Optimize, and Harmonize: Caring for Older Adults With Hematologic Malignancies.

Am Soc Clin Oncol Educ Book 2021 Mar;41:1-9

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA.

With the aging of the population, the number of older adults with hematologic malignancies is growing, and treatment paradigms for these patients are rapidly evolving. Use of allogeneic stem cell transplant has been expanding to include septuagenarians but remains a potentially morbid procedure, creating an opportunity for a geriatric-focused evaluation to improve assessment of the individual's risk in undergoing the procedure. Although age alone should not be the sole determinant for transplant eligibility, geriatric assessment often identifies vulnerabilities that are not captured in assessing performance status and comorbidities alone. Those vulnerabilities may be optimized in an approach employing three sequential steps: characterize resiliency, bolster resilience, and harmonize with patient goals. Data are emerging that show that this approach is associated with lower nonrelapse mortality, shorter length of stay, and better survival after transplant. In older adults with myeloma, treatment recommendations also aim to balance the expected efficacy and toxicity profile and incorporate the patient's goals and preferences. Assessment of frailty allows for more personalized estimates of risk of toxicity. Currently, the European Myeloma Network currently recommends using the International Myeloma Working Group frailty scale as a standard approach to defining frail or at-risk populations with myeloma. In addition to treatment selection, the care of older adults with myeloma must include consideration of other issues, including reducing early mortality with antibiotic prophylaxis, polypharmacy, depression, cognition, and falls. Overall, appreciation of the aging-associated vulnerabilities will allow for the ultimate personalized care and treatment of older adults with hematologic malignancies.
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http://dx.doi.org/10.1200/EDBK_320141DOI Listing
March 2021

Serious Adverse Events in Related Donors: A Report from the Related Donor Safe Study.

Transplant Cell Ther 2021 04 15;27(4):352.e1-352.e5. Epub 2021 Jan 15.

Children's Hospital Los Angeles Cancer and Blood Disease Institute, USC Keck School of Medicine, Los Angeles, California.

The incidence and risk factors for severe adverse events (SAEs) in related donors (RD) of hematopoietic cell transplants is unknown. The Related Donor Safe study is a prospective observational cohort of 1680 RDs and represents an opportunity to examine characteristics of SAEs in RDs. In this cohort, we found that SAEs were reported in a total 12 (0.71%) RDs. Of these, 5 SAEs occurred in bone marrow donors (5/404, 1.24%), and 7 (7/1276, 0.55%) were in donors of peripheral blood stem cells. All of the SAEs were considered to be related (definite, probable, or possible) to the donation process. There were no donor fatalities. Of the 12 RDs who experienced an SAE, 10 were either overweight or obese. Five of the 12 RDs had predonation medical conditions that would have resulted in either possible or definite ineligibility for donation were they being assessed as unrelated donors. These SAE data will be useful in the counseling of prospective RDs before planned donation and may be helpful in identifying donors who should be considered medically unsuitable for donation.
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http://dx.doi.org/10.1016/j.jtct.2021.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036235PMC
April 2021

Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin.

J Clin Oncol 2021 Mar 13;39(9):1001-1009. Epub 2021 Jan 13.

Leukemia Service, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY.

Purpose: Impaired response to erythropoietin underlies ineffective erythropoiesis and anemia in myelodysplastic syndromes (MDS). We investigated whether treatment with lenalidomide (LEN), which augments erythropoietin receptor signaling in vitro, can restore and improve hemoglobin response to epoetin (EPO) alfa in patients with lower-risk, non-del(5q) MDS who have anemia that is refractory to or have low probability of benefit from treatment with recombinant erythropoietin.

Methods: In a phase III, US intergroup trial, we randomly assigned patients to receive either LEN and EPO alfa or LEN alone following stratification by serum erythropoietin concentration and prior erythropoietin treatment.

Results: A total of 195 evaluable patients were randomly assigned: 99 patients to the LEN-EPO alfa cohort and 96 to LEN alone. After four cycles of treatment, the primary end point of major erythroid response (MER) was significantly higher (28.3%) with the combination compared with LEN alone (11.5%) ( = .004). Among 136 patients who completed 16 weeks of study treatment, 38.9% and 15.6% achieved MER, respectively ( = .004). Additionally, minor erythroid response was achieved in 18.2% and 20.8% of patients, for an overall erythroid response rate of 46.5% versus 32.3%. Among LEN nonresponders, 38 crossed over to the addition of EPO alfa with 10 patients (26.3%) achieving a MER. Responses to the combined treatment were highly durable with a median MER duration of 23.8 months compared with 13 months with LEN alone.

Conclusion: LEN restores sensitivity to recombinant erythropoietin in growth factor-insensitive, lower-risk, non-del(5q) MDS, to yield a significantly higher rate and duration of MER compared with LEN alone (funded by the National Cancer Institute; E2905 ClinicalTrials.gov identifier: NCT02048813).
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http://dx.doi.org/10.1200/JCO.20.01691DOI Listing
March 2021

Recommendations and outcomes from a geriatric assessment guided multidisciplinary clinic prior to autologous stem cell transplant in older patients.

J Geriatr Oncol 2021 May 5;12(4):585-591. Epub 2020 Nov 5.

City of Hope, Duarte, CA, United States of America.

Background: Autologous hematopoietic stem cell transplant (autoHCT) is a mainstay of treatment for multiple myeloma and non-Hodgkin lymphoma but is underutilized in older adults. We investigated the association of vulnerabilities identified by a geriatric assessment (GA)-guided multidisciplinary clinic (MDC) on the receipt of autoHCT and evaluated its ability to predict outcomes in older autoHCT candidates.

Methods: Patients 50+ years received GA-informed optimization recommendations: 'decline' if unlikely to realize benefits of autoHCT, 'defer' if optimization necessary before autoHCT, and 'proceed' if autoHCT could proceed without delay. We compared characteristics and outcomes of autoHCT recipients (n = 62) to non-autoHCT patients (n = 29) and evaluated GA deficits on outcomes.

Results: 91 patients were evaluated; the MDC recommendation was 'decline' for 5 (6%), 'defer' for 25 (27%), and 'proceed' for 61 (67%). AutoHCT recipients had fewer GA-rated impairments relative to non-autoHCT patients, as did patients with a 'proceed' recommendation relative to 'defer'. Among autoHCT recipients, 1-year and 3-year non-relapse morality (NRM) was 0% and 5%, and there was no difference in length of hospitalization, readmission rate, or mortality after transplant by MDC recommendation. Frail grip strength and poor performance status were associated with inferior post-autoHCT progression-free survival and overall survival.

Conclusions: Patients pursuing autoHCT after MDC-directed optimization achieved excellent outcomes, including patients deferred but ultimately receiving autoHCT. GA-identified functional deficits, especially frail grip strength, may improve risk stratification in older autoHCT candidates. Employing a GA earlier in the disease trajectory to inform early referral to an MDC may increase autoHCT safety and utilization in older patients.
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http://dx.doi.org/10.1016/j.jgo.2020.10.019DOI Listing
May 2021

Markers of Iron Flux during Testosterone-Mediated Erythropoiesis in Older Men with Unexplained or Iron-Deficiency Anemia.

J Clin Endocrinol Metab 2020 11;105(11)

Division of Endocrinology, Diabetes, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Context: Testosterone treatment of hypogonadal men improves their hemoglobin, but the mechanism is not understood.

Objective: To investigate possible mechanisms by which testosterone stimulates erythropoiesis in hypogonadal older men with unexplained or iron-deficiency anemia.

Design: The Anemia Trial of The Testosterone Trials, a placebo-controlled study in older, hypogonadal men.

Setting: Twelve academic medical centers.

Participants: A total of 95 hypogonadal men (testosterone < 275 ng/mL) ≥65 years with anemia (hemoglobin < 12.7 g/dL). They were classified as having unexplained (n = 58) or iron deficiency anemia (n = 37).

Intervention: Testosterone or placebo gel for 1 year.

Main Outcome Measures: Markers of iron metabolism during the first 3 months of treatment.

Results: Testosterone replacement significantly (P < 0.001) increased hemoglobin in the 58 men who had unexplained anemia (adjusted mean difference 0.58 g/dL; 95% confidence interval, 0.31-0.85). Testosterone replacement tended to increase hemoglobin in the 37 men who had iron deficiency (0.38 g/dL; -0.19, 0.95), but the response was more variable and not statistically significant (P = 0.19). In men with unexplained anemia, testosterone replacement suppressed hepcidin (-8.2 ng/mL; -13.7, -2.7; P = 0.004) and ferritin (-19.6 µg/L; -32.8, -6.3; P = 0.004), but in men with iron deficiency, testosterone replacement did not. The decrease in hepcidin was moderately correlated with the increase in hemoglobin in the men with unexplained anemia (correlation coefficient -0.35, P = 0.01) but not in those with iron deficiency anemia (correlation coefficient -0.07, P = 0.73).

Conclusions: Testosterone replacement of older hypogonadal men with unexplained anemia stimulates erythropoiesis associated with increased iron mobilization. This effect appears to be attenuated by iron deficiency.
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http://dx.doi.org/10.1210/clinem/dgaa521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500468PMC
November 2020

Hepatitis B Virus Screening and Management for Patients With Cancer Prior to Therapy: ASCO Provisional Clinical Opinion Update.

J Clin Oncol 2020 11 27;38(31):3698-3715. Epub 2020 Jul 27.

City of Hope Comprehensive Cancer Center, Duarte, CA.

Purpose: This Provisional Clinical Opinion update presents a clinically pragmatic approach to hepatitis B virus (HBV) screening and management.

Provisional Clinical Opinion: All patients anticipating systemic anticancer therapy should be tested for HBV by 3 tests-hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) total immunoglobulin (Ig) or IgG, and antibody to hepatitis B surface antigen-but anticancer therapy should not be delayed. Findings of chronic HBV (HBsAg-positive) or past HBV (HBsAg-negative and anti-HBc-positive) infection require HBV reactivation risk assessment.Patients with chronic HBV receiving any systemic anticancer therapy should receive antiviral prophylactic therapy through and for minimum 12 months following anticancer therapy. Hormonal therapy alone should not pose a substantial risk of HBV reactivation in patients with chronic HBV receiving hormonal therapy alone; these patients may follow noncancer HBV monitoring and treatment guidance. Coordination of care with a clinician experienced in HBV management is recommended for patients with chronic HBV to determine HBV monitoring and long-term antiviral therapy after completion of anticancer therapy.Patients with past HBV infection undergoing anticancer therapies associated with a high risk of HBV reactivation, such as anti-CD20 monoclonal antibodies or stem-cell transplantation, should receive antiviral prophylaxis during and for minimum 12 months after anticancer therapy completion, with individualized management thereafter. Careful monitoring may be an alternative if patients and providers can adhere to frequent, consistent follow-up so antiviral therapy may begin at the earliest sign of reactivation. Patients with past HBV undergoing other systemic anticancer therapies not clearly associated with a high risk of HBV reactivation should be monitored with HBsAg and alanine aminotransferase during cancer treatment; antiviral therapy should commence if HBV reactivation occurs.Additional information is available at www.asco.org/supportive-care-guidelines.
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http://dx.doi.org/10.1200/JCO.20.01757DOI Listing
November 2020

Phase I trial of maintenance selinexor after allogeneic hematopoietic stem cell transplantation for patients with acute myeloid leukemia and myelodysplastic syndrome.

Bone Marrow Transplant 2020 11 6;55(11):2204-2206. Epub 2020 May 6.

Section of Hematology/Oncology, University of Chicago Medicine, 5841S Maryland Ave, Chicago, IL, 60637, USA.

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http://dx.doi.org/10.1038/s41409-020-0925-2DOI Listing
November 2020

A phase 1 study of azacitidine with high-dose cytarabine and mitoxantrone in high-risk acute myeloid leukemia.

Blood Adv 2020 02;4(4):599-606

Comprehensive Cancer Center.

In this phase 1 study, azacitidine (AZA) was given before high-dose cytarabine (HiDAC) and mitoxantrone (mito) based on the hypothesis that epigenetic priming with a hypomethylating agent before cytotoxic chemotherapy would improve response rates in patients with high-risk acute myeloid leukemia (AML), including relapsed/refractory disease. The primary objective was to establish the recommended phase 2 dose of AZA given before standard HiDAC/mito. In a dose escalation scheme, 46 patients (median age, 66 years) received AZA at 37.5, 50, or 75 mg/m2 subcutaneously or IV once daily on days 1 to 5 followed by HiDAC (3000 mg/m2) and mitoxantrone (30 mg/m2) once each on days 6 and 10 (the HiDAC/mito dose was reduced 33% in elderly subjects). Two dose-limiting toxicities occurred (both in the same patient): acute liver failure and kidney injury at the 50 mg/m2 dose. The 30-day induction death rate was 2.2% (1 of 46). The overall response rate, including complete remission and complete remission with incomplete count recovery, was 61% (28 of 46). Previously untreated patients aged ≥60 years with therapy-related AML and de novo AML were more likely to respond than untreated patients with AML progressing from an antecedent hematologic disorder (myelodysplastic syndrome and chronic myelomonocytic leukemia). Patients with favorable European Leukemia Network risk (P = .008), NPM1 mutations (P = .007), or IDH2 mutations (P = .03) were more likely to respond, and those with TP53 mutations (P = .03) were less likely to respond. The recommended phase 2 dose of AZA is 75 mg/m2 per day on days 1 to 5 followed by HiDAC (3000 mg/m2) and mitoxantrone (30 mg/m2) once each on days 6 and 10. This trial was registered at www.clinicaltrials.gov as #NCT01839240.
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http://dx.doi.org/10.1182/bloodadvances.2019000795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042987PMC
February 2020

Dose escalation prophylactic donor lymphocyte infusion after T-cell depleted matched related donor allogeneic hematopoietic cell transplantation is feasible and results in higher donor chimerism, faster immune re-constitution, and prolonged progression-free survival.

Bone Marrow Transplant 2020 06 28;55(6):1161-1168. Epub 2020 Jan 28.

Section of Hematology/Oncology, Department of Medicine and Comprehensive Cancer Center, University of Chicago, Chicago, IL, USA.

Prophylactic donor lymphocyte infusion (pDLI) is a potential intervention to prolong remission for patients receiving allogeneic hematopoietic stem cell transplantation (allo-SCT), however, the optimal timing and dose are unknown. We conducted a prospective trial exploring the feasibility of early withdrawal of immunosuppression (WOI) at day 60 followed by dose escalation of pDLI after alemtuzumab-based, T-cell depleted conditioning for patients with high-risk hematologic malignancies. pDLI were administered at day 75 to day 90 and again in 4-8 week intervals with receipt of up to 5 pDLI infusions. Fourty-six patients with matched-related donors (MRD) and 29 patients with matched-unrelated donors (MUD) were considered. Twenty-eight MRD patients were able to undergo WOI, 26 patients (93%) received at least 1 DLI, 16 patients (57%) received 3+, and 7 patients (25%) received 5 pDLI. Only 7 MUD patients were able to undergo WOI, 4 (57%) received at least 1 pDLI, 1 patient (14%) received 3 DLI, and no patients received all 5. Median PFS for patients on the study was 366 days. The estimated 2-year PFS and OS rates for all patients were 41% (95% CI, 32-54%) and 51% (95% CI, 41-63%) compared with 57% (95% CI, 41-77%) and 67% (95% CI, 52-86%) for patients who received at least one pDLI. In addition, MRD patients receiving pDLI had faster immune re-constitution and improved donor chimerism. Our trial proposes a novel dosage and treatment schedule for pDLI that is tolerable for patients who have received MRD allo-SCT and leads to improved outcomes.
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http://dx.doi.org/10.1038/s41409-020-0798-4DOI Listing
June 2020

Results from a multidisciplinary clinic guided by geriatric assessment before stem cell transplantation in older adults.

Blood Adv 2019 11;3(22):3488-3498

Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA.

Limitations found on geriatric assessment (GA) track with worse outcomes after hematopoietic cell transplantation (HCT). We report on a multidisciplinary team clinic (MDC), consisting of a cancer-specific GA and a multidisciplinary team of providers, to assess candidacy and create an individualized optimization plan for allogeneic HCT candidates aged ≥60 years and autologous HCT and adoptive T-cell therapy candidates aged ≥70 years. Among the 247 patients evaluated in the MDC, allogeneic HCT candidates comprised the majority (60%), followed by autologous HCT (37%) with occasional older cellular therapy candidates (3%). Almost all patients meeting program-required minimum ages for MDC optimization at our institution were assessed (98%). Relative to historical control subjects undergoing GA alone, allogeneic HCT patients aged ≥60 years who underwent MDC appraisal had similar frequencies of high-risk disease, reduced intensity regimens, and high comorbidity but fewer GA-graded functional impairments. The MDC cohort experienced fewer inpatient deaths, shorter length of stay, and fewer discharges to nursing facilities compared with control subjects. Improvements in early mortality were observed over time; 1-year overall survival improved from 43% in the pre-MDC era to 70% in the recent MDC era, and 1-year nonrelapse mortality decreased from 43% to 18%. The 31 autologous HCT recipients aged ≥70 years optimized by the MDC achieved 0% nonrelapse mortality and 97% overall survival at 1 year. A GA-guided MDC for older HCT candidates is feasible and seems to reduce transplant-associated morbidity and mortality. An MDC should encourage broader and safer utilization of transplantation in older patients.
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http://dx.doi.org/10.1182/bloodadvances.2019000790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880895PMC
November 2019

Effective desensitization for a strong donor-specific HLA antibody in a case of HLA-mismatched allogeneic hematopoietic cell transplantation.

HLA 2019 09 6;94(3):307-311. Epub 2019 Aug 6.

Department of Pathology, The University of Chicago Medicine, Chicago, Illinois.

We describe a unique ABO compatible and 9/10 HLA-matched case of successful allogeneic hematopoietic cell transplantation (HCT) after effective desensitization of a strong anti-HLA-A24 donor-specific antibody (DSA) with mean fluorescence intensity of approximately 18 000. Due to absence of a suitable matched unrelated donor the patient sibling was considered the best available donor, and it was decided to desensitize patient prior to transplant. The strength of HLA-A24 DSA slowly decreased over the course of treatment, necessitating a total of 23 sessions of therapeutic plasma exchange in order to bring the DSA strength to undetectable levels, followed by a successful transplant. In summary, the outcome of this case shows effective application of desensitization treatment to remove strong DSA in HCT patients.
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http://dx.doi.org/10.1111/tan.13627DOI Listing
September 2019

Allogeneic hematopoietic cell transplantation compared to chemotherapy consolidation in older acute myeloid leukemia (AML) patients 60-75 years in first complete remission (CR1): an alliance (A151509), SWOG, ECOG-ACRIN, and CIBMTR study.

Leukemia 2019 11 9;33(11):2599-2609. Epub 2019 May 9.

City of Hope, Duarte, CA, USA.

The preferred post-remission therapy for older patients with acute myeloid leukemia (AML) in first complete remission (CR1) remains uncertain. In this retrospective, multicenter study, we compared the outcomes for older AML patients (age 60-77 years) receiving allogeneic hematopoietic cell transplantation (alloHCT) (n = 431) with those treated on prospective National Clinical Trials Network induction and nontransplantation chemotherapy (CT) consolidation trials (n = 211). AlloHCT patients were younger (median age: 64.2 versus 67.9 years, p < 0.001), but more frequently had high-risk AML (high WBC, secondary AML, and unfavorable cytogenetics). Overall survival (OS) was worse in alloHCT during the first 9 months after CR1 (HR = 1.52, p = 0.02), but was significantly better thereafter (HR = 0.53, p < 0.0001) relative to CT. Treatment-related mortality (TRM) following HCT was worse in the first 9 months (HR = 2.8, 95% CI: 1.5-5.2, p = 0.0009), while post-HCT relapse was significantly less frequent beyond 9 months (HR = 0.42, 95% CI: 0.29-0.61, p < 0.0001). Despite higher early TRM, alloHCT recipients had superior long-term OS [29% (24-34%) versus CT 13.8% (9-21%) at 5 years]. Although this is a retrospective analysis with potential biases, it indicates that alloHCT led to heightened early risks from TRM, yet reduced relapse and superior long-term survival relative to CT in older AML patients in CR1.
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http://dx.doi.org/10.1038/s41375-019-0477-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842042PMC
November 2019

Plerixafor alone for the mobilization and transplantation of HLA-matched sibling donor hematopoietic stem cells.

Blood Adv 2019 03;3(6):875-883

Center for International Blood and Marrow Transplant Research, National Marrow Donor Program/Be The Match, Minneapolis, MN.

Plerixafor, a direct antagonist of CXCR4/stromal-derived factor 1, can safely and rapidly mobilize allografts without the use of granulocyte colony-stimulating factor (G-CSF). We conducted a phase 2, multicenter, prospective study of plerixafor-mobilized HLA-identical sibling allografts for allogeneic hematopoietic cell transplantation in recipients with hematological malignancies. Donors (n = 64) were treated with subcutaneous plerixafor (240 µg/kg) and started leukapheresis (LP) 4 hours later. The primary objective was to determine the proportion of donors who were successfully mobilized: defined as collection of ≥2.0 × 10 CD34 cells per kilogram recipient weight in ≤2 LP sessions. Recipients subsequently received reduced intensity (RIC; n = 33) or myeloablative (MAC; n = 30) conditioning. Sixty-three of 64 (98%) donors achieved the primary objective. The median CD34 cell dose per kilogram recipient weight collected within 2 days was 4.7 (0.9-9.6). Plerixafor was well tolerated with only grade 1 or 2 drug-related adverse events noted. Bone pain was not observed. Plerixafor-mobilized grafts engrafted promptly. One-year progression-free and overall survivals were 53% (95% confidence interval [CI], 36% to 71%) and 63% (95% CI, 46% to 79%) for MAC and 64% (95% CI, 47% to 79%) and 70% (95% CI, 53% to 84%) for RIC recipients, respectively. Donor toxicity was reduced relative to G-CSF mobilized related donors. This is the first multicenter trial to demonstrate that, as an alternative to G-CSF, plerixafor rapidly and safely mobilizes sufficient numbers of CD34 cells from matched sibling donors for HCT. Engraftment was prompt, and outcomes in recipients were encouraging. This trial was registered at clinicaltrials.gov as #NCT01696461.
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http://dx.doi.org/10.1182/bloodadvances.2018027599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436017PMC
March 2019

Outcomes following second allogeneic stem cell transplant for disease relapse after T cell depleted transplant correlate with remission status and remission duration after the first transplant.

Exp Hematol Oncol 2019 3;8. Epub 2019 Jan 3.

2Department of Medicine, Section of Hematology/Oncology, The University of Chicago Medical Center, 5841 S. Maryland, MC 2115, Chicago, IL 60637-1470 USA.

Background: Second allogeneic hematopoietic stem cell transplant (HCT) remains as an option for disease relapse after initial HCT.

Methods: We analyzed retrospectively the outcomes of 65 consecutive patients who underwent a second HCT for disease relapse at the University of Chicago. Univariate and multivariate analysis were conducted, and a scoring system was generated to select the patients who would benefit second HCT.

Results: All except four patients received T cell depleted (TCD) first HCT. The majority of patients had AML (n = 47) and high risk MDS (n = 5). The median age at second HCT was 45 years (11-73). 13 patients (20%) achieved CR before second HCT. 98% (n = 64) and 72% (n = 47) patients achieved neutrophil and platelet engraftment at a median interval of 10 and 18 days, respectively, following the second HCT. With a median follow up of 23 (5.5-140) months for survivors after second HCT, the estimated 2 years PFS was 17.5% and the 2 years OS was 22.6%. The day 100 cumulative incidence of non-relapse mortality rate was 23.6%, and the cumulative incidence of aGVHD and cGVHD were 16.9% and 7.7% respectively at 1 year after second HCT. In univariate analysis, patients with remission duration after first HCT of > 12 months and those in CR before second HCT had significantly better PFS and OS. A scoring system using disease status before second HCT (CR = 0 vs. non-CR = 1), and remission duration after first HCT (< 6 = 2, 6-12 = 1 and > 12 months = 0) was generated as an approach to classify patients into different risk categories in the purpose to provide guidance to the transplant physician to inform the outcomes to potential patients undergoing 2nd HCT. A score of < 2 (n = 26) identified a group with PFS and OS of 31.6% and 36.2% at 2 years after second HCT.

Conclusion: In conclusion, second HCT is a viable option for disease relapse after TCD HCT for patients entering second HCT in remission and/or remission duration > 12 months after first HCT with acceptable rates of GVHD and donor engraftment.
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http://dx.doi.org/10.1186/s40164-018-0125-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317199PMC
January 2019

Effect of Aging and Predonation Comorbidities on the Related Peripheral Blood Stem Cell Donor Experience: Report from the Related Donor Safety Study.

Biol Blood Marrow Transplant 2019 04 10;25(4):699-711. Epub 2018 Nov 10.

Doernbecher Children's Hospital, Oregon Health & Science University, Portland, Oregon.

The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study. RDs aged > 60 had a lower median CD34 level before apheresis compared with younger RDs (age > 60, 59 × 10/L; age 41 to 60, 81 × 10/L; age 18 to 40, 121 × 10/L; P < .001). This resulted in older donors undergoing more apheresis procedures (49% versus 30% ≥ 2 collections, P < .001) and higher collection volumes (52% versus 32% > 24 L, P < .001), leading to high percentages of donors aged > 60 with postcollection thrombocytopenia <50 × 10/L (26% and 57% after 2 and 3days of collection, respectively). RDs aged 18 to 40 had a higher risk of grades 2 to 4 pain and symptoms pericollection, but donors over age 40 had more persistent pain at 1, 6, and 12 months (odds ratio [OR], 1.7; P = 0.02) and a higher rate of nonrecovery to predonation levels (OR, 1.7; P = .01). Donors reporting comorbidities increased significantly with age, and those with comorbidities that would have led to deferral by National Marrow Donor Program unrelated donor standards had an increased risk for persistent grades 2 to 4 pain (OR, 2.41; P < .001) and failure to recover to predonation baseline for other symptoms (OR, 2.34; P = .004). This information should be used in counseling RDs regarding risk and can assist in developing practice approaches aimed at improving the RD experience for high-risk individuals.
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http://dx.doi.org/10.1016/j.bbmt.2018.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453753PMC
April 2019

Related peripheral blood stem cell donors experience more severe symptoms and less complete recovery at one year compared to unrelated donors.

Haematologica 2019 04 31;104(4):844-854. Epub 2018 Oct 31.

Memorial Sloan Kettering Cancer Center - Adult, New York, NY.

Unlike unrelated donor registries, transplant centers lack uniform approaches to related donor assessment and deferral. To test whether related donors are at increased risk for donation-related toxicities, we conducted a prospective observational trial of 11,942 related and unrelated donors aged 18-60 years. Bone marrow (BM) was collected at 37 transplant and 78 National Marrow Donor Program centers, and peripheral blood stem cells (PBSC) were collected at 42 transplant and 87 unrelated donor centers in North America. Possible presence of medical comorbidities was verified prior to donation, and standardized pain and toxicity measures were assessed pre-donation, peri-donation, and one year following. Multivariate analyses showed similar experiences for BM collection in related and unrelated donors; however, related stem cell donors had increased risk of moderate [odds ratios (ORs) 1.42; <0.001] and severe (OR 8.91; <0.001) pain and toxicities (OR 1.84; <0.001) with collection. Related stem cell donors were at increased risk of persistent toxicities (OR 1.56; =0.021) and non-recovery from pain (OR 1.42; =0.001) at one year. Related donors with more significant comorbidities were at especially high risk for grade 2-4 pain (OR 3.43; <0.001) and non-recovery from toxicities (OR 3.71; <0.001) at one year. Related donors with more significant comorbidities were at especially high risk for grade 2-4 pain (OR 3.43; <0.001) and non-recovery from toxicities (OR 3.71; <0.001) at one year. Related donors reporting grade ≥2 pain had significant decreases in Health-Related Quality of Life (HR-QoL) scores at one month and one year post donation (=0.004). In conclusion, related PBSC donors with comorbidities are at increased risk for pain, toxicity, and non-recovery at one year after donation. Risk profiles described in this study should be used for donor education, planning studies to improve the related donor experience, and decisions regarding donor deferral. Registered at .
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http://dx.doi.org/10.3324/haematol.2018.200121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442962PMC
April 2019

Characterization of cancer comorbidity prior to allogeneic hematopoietic cell transplantation.

Leuk Lymphoma 2019 03 2;60(3):629-638. Epub 2018 Aug 2.

a Department of Medicine , University of Chicago , Chicago , IL , USA.

Higher comorbidity by the hematopoietic cell transplantation-comorbidity index increases rates of non-relapse mortality (NRM) and impairs survival following allogeneic hematopoietic transplantation. We explored the effects of cancer as a comorbid condition prior to allogeneic transplantation. Among 356 adult transplant recipients, 54 patients (15%) had 58 comorbid cancers. Among 33 solid cancers (9%), breast (n = 12; 20%) was most common; among 26 comorbid hematologic malignancies (i.e. separate hematologic malignancy not related to primary disease) (7%), lymphoma was most common (n = 14; 24%). In unadjusted analysis, increased risks for NRM were found for cancer comorbidity (HR 2.1, p < .001), solid tumor alone (HR 2.1, p < .001), and hematologic malignancy alone (HR 1.9, p = .03). Cancer comorbidity did not impair 2-year overall survival (HR 1.33, CI 0.92-1.94). Both hematologic and solid cancers likely contribute to elevated risks of nonrelapse mortality, unrelated to recurrence of the cancer comorbidity. Further study is indicated to validate these findings.
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http://dx.doi.org/10.1080/10428194.2018.1493728DOI Listing
March 2019

Screening for Hepatitis B Virus Infection: Are We Asking the Right Questions?

J Clin Oncol 2018 04 22;36(10):935-936. Epub 2018 Feb 22.

Andrew S. Artz and Sonali Paul, University of Chicago, Chicago, IL.

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http://dx.doi.org/10.1200/JCO.2018.77.7128DOI Listing
April 2018

A phase I study of selinexor in combination with high-dose cytarabine and mitoxantrone for remission induction in patients with acute myeloid leukemia.

J Hematol Oncol 2018 01 5;11(1). Epub 2018 Jan 5.

Department of Medicine, Section of Hematology/Oncology, University of Chicago Medicine, 5841 S. Maryland, MC 2115, Chicago, IL, 60637-1470, USA.

Background: Novel therapies for patients with acute myeloid leukemia (AML) are imperative, particularly for those with high-risk features. Selinexor, an exportin 1 (XPO1/CRM1) inhibitor, has demonstrated anti-leukemia activity as a single agent, as well as in combination with anthracyclines and/or DNA-damaging agents.

Methods: We report the findings of a phase I dose escalation trial with cohort expansion in 20 patients with newly diagnosed or relapsed/refractory AML that combined selinexor with age-adjusted high-dose cytarabine and mitoxantrone (HiDAC/Mito).

Results: Three (15%) patients received the initial dose of 60 mg of selinexor (~ 35 mg/m), and 17 (85%) received the target level of 80 mg (~ 50 mg/m). No dose-limiting toxicities were observed. Common adverse events included febrile neutropenia (70%), diarrhea (40%), anorexia (30%), electrolyte abnormalities (30%), bacteremia (25%), cardiac toxicities (25%), fatigue (25%), and nausea/vomiting (25%). None were unexpected given the HiDAC/Mito regimen. Serious adverse events occurred in 6 (30%) patients; one was fatal. Ten (50%) patients achieved a complete remission (CR), 3 (15%) achieved CR with incomplete recovery (CRi), 1 (5%) achieved partial remission (PR), and 6 (30%) had progressive disease for an overall response rate (ORR) of 70%. Eight of 14 (57%) responders proceeded to allogeneic stem cell transplantation. Correlative studies of WT1 levels showed persistently detectable levels in patients who either did not respond or relapsed quickly after induction.

Conclusion: The selinexor/HiDAC/Mito regimen is feasible and tolerable at selinexor doses of 80 mg/day (~ 50 mg/m/day) twice weekly. The recommended phase II dose is 80 mg and warrants further study in this combination.

Trial Registration: ClinicalTrials.gov , NCT02573363 . Registered October 5, 2015.
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http://dx.doi.org/10.1186/s13045-017-0550-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756334PMC
January 2018

Reduced-Intensity Allogeneic Transplant for Acute Myeloid Leukemia and Myelodysplastic Syndrome Using Combined CD34-Selected Haploidentical Graft and a Single Umbilical Cord Unit Compared with Matched Unrelated Donor Stem Cells in Older Adults.

Biol Blood Marrow Transplant 2018 05 27;24(5):997-1004. Epub 2017 Dec 27.

Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois. Electronic address:

Haplo/cord transplantation combines an umbilical cord blood (UCB) graft with CD34-selected haploidentical cells and results in rapid hematopoietic recovery followed by durable UCB engraftment. We compared outcomes of transplants in older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) who received either HLA-matched unrelated donor (MUD) cells or haplo/cord grafts. Between 2007 and 2013, 109 adults ages 50 and older underwent similar reduced-intensity conditioning with fludarabine and melphalan and antibody-mediated T cell depletion for AML (n = 83) or high-risk MDS (n = 26) followed by either a MUD (n = 68) or haplo/cord (n = 41) graft. Patient characteristics were similar for each graft source except for more minority patients receiving a haplo/cord transplant (P = .01). One half of the AML patients were not in remission. Two-year progression-free survival (PFS), overall survival (OS), and graft-versus-host disease-free relapse-free survival were 38%, 48%, and 32.1% for MUD and 33%, 48%, and 33.8% for haplo/cord transplants (P = .62 for PFS; P = .97 for OS; P= .84), respectively. Acute grades II to IV and chronic graft-versus-host-disease rates did not differ at 19.5% and 4.9% in haplo/cord compared with 25% and 7.4% after MUD (P = .53 and P = .62, respectively). Multivariate analysis confirmed no significant differences in transplant outcomes by donor type. Haplo/cord reduced-intensity transplantation achieves similar outcomes relative to MUD in older AML and MDS patients, making this a promising option for those without matched donors.
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http://dx.doi.org/10.1016/j.bbmt.2017.12.794DOI Listing
May 2018

Association of Testosterone Levels With Anemia in Older Men: A Controlled Clinical Trial.

JAMA Intern Med 2017 04;177(4):480-490

Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.

Importance: In one-third of older men with anemia, no recognized cause can be found.

Objective: To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration.

Design, Setting, And Participants: A double-blinded, placebo-controlled trial with treatment allocation by minimization using 788 men 65 years or older who have average testosterone levels of less than 275 ng/dL. Of 788 participants, 126 were anemic (hemoglobin ≤12.7 g/dL), 62 of whom had no known cause. The trial was conducted in 12 academic medical centers in the United States from June 2010 to June 2014.

Interventions: Testosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months.

Main Outcomes And Measures: The percent of men with unexplained anemia whose hemoglobin levels increased by 1.0 g/dL or more in response to testosterone compared with placebo. The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors.

Results: The men had a mean age of 74.8 years and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30.7; 84.9% were white. Testosterone treatment resulted in a greater percentage of men with unexplained anemia whose month 12 hemoglobin levels had increased by 1.0 g/dL or more over baseline (54%) than did placebo (15%) (adjusted OR, 31.5; 95% CI, 3.7-277.8; P = .002) and a greater percentage of men who at month 12 were no longer anemic (58.3%) compared with placebo (22.2%) (adjusted OR, 17.0; 95% CI, 2.8-104.0; P = .002). Testosterone treatment also resulted in a greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by 1.0 g/dL or more (52%) than did placebo (19%) (adjusted OR, 8.2; 95% CI, 2.1-31.9; P = .003). Testosterone treatment resulted in a hemoglobin concentration of more than 17.5 g/dL in 6 men who had not been anemic at baseline.

Conclusions And Relevance: Among older men with low testosterone levels, testosterone treatment significantly increased the hemoglobin levels of those with unexplained anemia as well as those with anemia from known causes. These increases may be of clinical value, as suggested by the magnitude of the changes and the correction of anemia in most men, but the overall health benefits remain to be established. Measurement of testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of low testosterone levels.

Trial Registration: clinicaltrials.gov Identifier: NCT00799617.
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http://dx.doi.org/10.1001/jamainternmed.2016.9540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433757PMC
April 2017

Biologic vs physiologic age in the transplant candidate.

Authors:
Andrew S Artz

Hematology Am Soc Hematol Educ Program 2016 Dec;2016(1):99-105

Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL.

Hematopoietic cell transplantation (HCT) remains a cornerstone of treatment of many hematologic malignancies but transplant-associated morbidity and mortality limit application to older patients. Biologic or chronologic age barriers to HCT have fallen, because patients in their 8th decade of life comprise the group with the greatest rise in transplant use over the past decade. Evaluating physiologic age or general health in older transplant candidates requires a systematic approach inclusive of functional and comorbidity assessment, which typically is accomplished through geriatric assessment (GA). GA incorporates measures of comorbidity, function, nutrition, social support, and other health-related domains to better describe physiologic age. Older allogeneic transplant patients have a surprisingly high prevalence of vulnerabilities by GA prior to transplant, and significant comorbidity or functional limitations heighten the risks of transplant-related mortality. Ultimately, incorporation of physiologic age can improve estimates of nondisease life expectancy, prognostic survival after HCT, and inform HCT candidacy. Future research on the optimal tools to characterize physiologic age and appropriate interventions in the context of transplant are needed.
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http://dx.doi.org/10.1182/asheducation-2016.1.99DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142444PMC
December 2016

The prognostic value of serum C-reactive protein, ferritin, and albumin prior to allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndromes.

Haematologica 2016 11 4;101(11):1426-1433. Epub 2016 Aug 4.

CIBMTR, (Center for International Blood and Marrow Transplant Research), Department of Medicine, Milwaukee, WI, USA.

We sought to confirm the prognostic importance of simple clinically available biomarkers of C-reactive protein, serum albumin, and ferritin prior to allogeneic hematopoietic cell transplantation. The study population consisted of 784 adults with acute myeloid leukemia in remission or myelodysplastic syndromes undergoing unrelated donor transplant reported to the Center for International Blood and Marrow Transplant Research. C-reactive protein and ferritin were centrally quantified by ELISA from cryopreserved plasma whereas each center provided pre-transplant albumin. In multivariate analysis, transplant-related mortality was associated with the pre-specified thresholds of C-reactive protein more than 10 mg/L (P=0.008) and albumin less than 3.5 g/dL (P=0.01) but not ferritin more than 2500 ng/mL. Only low albumin independently influenced overall mortality. Optimal thresholds affecting transplant-related mortality were defined as: C-reactive protein more than 3.67 mg/L, log(ferritin), and albumin less than 3.4 g/dL. A 3-level biomarker risk group based on these values separated risks of transplant-related mortality: low risk (reference), intermediate (HR=1.66, P=0.015), and high risk (HR=2.7, P<0.001). One-year survival was 74%, 67% and 56% for low-, intermediate- and high-risk groups. Routinely available pre-transplant biomarkers independently risk-stratify for transplant-related mortality and survival.
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http://dx.doi.org/10.3324/haematol.2016.145847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394859PMC
November 2016

Survivorship care for older adults with cancer: U13 conference report.

J Geriatr Oncol 2016 07;7(4):305-12

Division of Nursing Research and Education, City of Hope, Duarte, CA, USA.

Older adult cancer survivors currently account for almost 60% of all cancer survivors. The number of older cancer survivors will continue to increase as the population ages and as patients' live longer after a cancer diagnosis. As part of cancer center accreditation, the American College of Surgeons Commission on Cancer® (CoC) has placed great importance on survivorship care planning. While the CoC has set standards for general survivorship care, there is sparse evidence on how to best care for older adult cancer survivors. Concern exists among the medical community that survivorship care plans could increase paperwork without improving outcomes. Given the diverse and unique needs of older adult cancer survivors, the inter-professional team provides a structure and process for survivorship care built around the particular needs of older adults. The Cancer and Aging Research Group (CARG), in partnership with the NIA/NCI, held a U13 conference in May 2015 in part to discuss survivorship care for older adults with cancer. This report discusses four themes that emerged from one section of the conference: (1) survivorship care is a process that continually evolves to meet the needs of older adults; (2) older adult cancer survivors have unique needs and care plans should be tailored to meet these needs; (3) the inter-professional team is ideally suited to structure survivorship care of older adults; (4) patient advocacy must be encouraged throughout the cancer care continuum. As evidence based survivorship practices develop, the unique needs of older adults need to be given substantial attention.
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http://dx.doi.org/10.1016/j.jgo.2016.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969136PMC
July 2016

Frequency and Risk Factors Associated with Cord Graft Failure after Transplant with Single-Unit Umbilical Cord Cells Supplemented by Haploidentical Cells with Reduced-Intensity Conditioning.

Biol Blood Marrow Transplant 2016 06 19;22(6):1065-1072. Epub 2016 Feb 19.

Section of Hematology/Oncology, Department of Medicine, University of Chicago Medical Center, Chicago, Illinois.

Delayed engraftment and cord graft failure (CGF) are serious complications after unrelated cord blood (UCB) hematopoietic stem cell transplantation (HSCT), particularly when using low-cell-dose UCB units. The haplo-cord HSCT approach allows the use of a lower dose single UCB unit by co-infusion of a CD34(+) selected haploidentical graft, which provides early transient engraftment while awaiting durable UCB engraftment. We describe the frequency, complications, and risk factors of CGF after reduced-intensity conditioning haplo-cord HSCT. Among 107 patients who underwent haplo-cord HSCT, 94 were assessable for CGF, defined as <5% cord blood chimerism at day 60 in the myeloid and CD3 compartments, irrespective of neutrophil and platelet counts. CGF occurred in 14 of 94 assessable patients (15%). Median survival after CGF was 12.7 months with haploidentical or mixed haploidentical-autologous hematopoiesis persisting in the 7 surviving. Median progression-free survival after CGF was 7.7 months and was not statistically different from those without CGF (10.47 months; P = .18). In univariate analyses, no UCB factors were associated with CGF, including cell dose, cell viability, recipient major ABO mismatch against the UCB unit, or degree of HLA match. We also found no association of CGF with recipient cytomegalovirus serostatus, haploidentical donor age, or day 30 haploidentical chimerism. However, higher haploidentical total nucleated and CD34(+) cell doses and day 30 UCB chimerism < 5% in either the myeloid or CD3 compartments were associated with greater risk of CGF. We conclude that assessing chimerism at day 30 may foretell impending CGF, and avoidance of high haploidentical cell doses may reduce risk of CGF after haplo-cord HSCT. However, long-term survival is possible after CGF because of predominant haploidentical or mixed chimerism and hematopoietic function.
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http://dx.doi.org/10.1016/j.bbmt.2016.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867292PMC
June 2016

Incidence and predictors of respiratory viral infections by multiplex PCR in allogeneic hematopoietic cell transplant recipients 50 years and older including geriatric assessment.

Leuk Lymphoma 2016 08 24;57(8):1807-13. Epub 2015 Dec 24.

a Department of Medicine , University of Chicago ;

Community respiratory viruses (CRV) are important agents of morbidity and mortality within the allogeneic hematopoietic stem cell transplant (HCT) population. Few proven methods to prevent CRV infections exist. No studies have specifically investigated their impact on older patients. We reviewed patients 50 years and older undergoing HCT between 2009-2013 to determine the incidence of CRV infection using multiplex PCR and risk factors for infection including geriatric assessment (GA). Thirty-two first episode CRV infections occurred in 118 patients for a 1-year cumulative incidence of 27.2% (CI: 19.4-35.6%). Hospitalization and mortality were restricted to those who developed lower respiratory tract infections (LRTI) (n = 22, 69%). CRV infection contributed to 8 deaths (36% of LRTIs) and 7 of these patients were taking steroids for GvHD at the time of infection. Health impairments by GA did not translate into increased risk for CRV infection. Steroid use at time of LRTI was associated with high mortality.
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http://dx.doi.org/10.3109/10428194.2015.1113279DOI Listing
August 2016

Reply to J. Cabezas et al.

J Clin Oncol 2016 Jan 7;34(3):290-1. Epub 2015 Dec 7.

University of Chicago, Chicago, IL.

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http://dx.doi.org/10.1200/JCO.2015.64.3064DOI Listing
January 2016

Analysis of the Effect of Race, Socioeconomic Status, and Center Size on Unrelated National Marrow Donor Program Donor Outcomes: Donor Toxicities Are More Common at Low-Volume Bone Marrow Collection Centers.

Biol Blood Marrow Transplant 2015 Oct 23;21(10):1830-8. Epub 2015 Jun 23.

Division of Hematology, Oncology, and Blood and Marrow Transplantation, Children's Hospital of Los Angeles, USC Keck School of Medicine, Los Angeles, CA.

Previous studies have shown that risks of collection-related pain and symptoms are associated with sex, body mass index, and age in unrelated donors undergoing collection at National Marrow Donor Program centers. We hypothesized that other important factors (race, socioeconomic status [SES], and number of procedures at the collection center) might affect symptoms in donors. We assessed outcomes in 2726 bone marrow (BM) and 6768 peripheral blood stem cell (PBSC) donors collected between 2004 and 2009. Pain/symptoms are reported as maximum levels over mobilization and collection (PBSC) or within 2 days of collection (BM) and at 1 week after collection. For PBSC donors, race and center volumes were not associated with differences in pain/symptoms at any time. PBSC donors with high SES levels reported higher maximum symptom levels 1 week after donation (P = .017). For BM donors, black males reported significantly higher levels of pain (OR, 1.90; CI, 1.14 to 3.19; P = .015). No differences were noted by SES group. BM donors from low-volume centers reported more toxicity (OR, 2.09; CI, 1.26 to 3.46; P = .006). In conclusion, race and SES have a minimal effect on donation-associated symptoms. However, donors from centers performing ≤ 1 BM collection every 2 months have more symptoms after BM donation. Approaches should be developed by registries and low-volume centers to address this issue.
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http://dx.doi.org/10.1016/j.bbmt.2015.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568129PMC
October 2015

Hepatitis B Virus Screening for Patients With Cancer Before Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update.

J Oncol Pract 2015 Jul 19;11(4):e487-9. Epub 2015 May 19.

The University of Texas MD Anderson Cancer Center, Houston, TX; University of Chicago, Chicago, IL; and American Society of Clinical Oncology, Alexandria, VA.

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http://dx.doi.org/10.1200/JOP.2015.004846DOI Listing
July 2015