Publications by authors named "William J Hogan"

203 Publications

An adapted European LeukemiaNet genetic risk stratification for acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplant. A CIBMTR analysis.

Bone Marrow Transplant 2021 Sep 28. Epub 2021 Sep 28.

Division of Hematology/BMT, Mayo Clinic, Rochester, MN, USA.

Cytogenetic and molecular abnormalities are known to influence post-transplant outcomes in acute myeloid leukemia (AML) but data assessing the prognostic value of combined genetic models in the HCT setting are limited. We developed an adapted European LeukemiaNet (aELN) risk classification based on available genetic data reported to the Center for International Blood and Marrow Transplant Research, to predict post-transplant outcomes in 2289 adult AML patients transplanted in first remission, between 2013 and 2017. Patients were stratified according to aELN into three groups: favorable (Fav, N = 181), intermediate (IM, N = 1185), and adverse (Adv, N = 923). Univariate analysis demonstrated significant differences in 2-year overall survival (OS) (Fav: 67.7%, IM: 64.9% and Adv: 53.9%; p < 0.001); disease-free survival (DFS) (Fav: 57.8%, IM: 55.5% and Adv: 45.3; p < 0.001) and relapse (Fav: 28%, IM: 27.5% and Adv: 37.5%; p < 0.001). Multivariate analysis (MVA) revealed no differences in outcomes between the Fav and IM groups, thus they were combined. On MVA, patients in the Adv risk group had the highest risk of relapse (HR 1.47 p ≤ 0.001) and inferior DFS (HR 1.35 p < 0.001) and OS (HR 1.39 p < 0.001), even using myeloablative conditioning or in those without the pre-HCT measurable-residual disease. Novel approaches to mitigate relapse in this high-risk group are urgently needed.
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http://dx.doi.org/10.1038/s41409-021-01450-3DOI Listing
September 2021

Isolated T-cell acute lymphoblastic leukemic optic disc infiltration.

Am J Hematol 2021 Sep 24. Epub 2021 Sep 24.

Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

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http://dx.doi.org/10.1002/ajh.26357DOI Listing
September 2021

Spectrum of hematological malignancies, clonal evolution and outcomes in 144 Mayo Clinic patients with germline predisposition syndromes.

Am J Hematol 2021 Nov 27;96(11):1450-1460. Epub 2021 Aug 27.

Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.

Germline predisposition syndromes (GPS) result from constitutional aberrations in tumor suppressive and homeostatic genes, increasing risk for neoplasia in affected kindred. In this study, we present clinical and genomic data on 144 Mayo Clinic patients with GPS; 59 evaluated prospectively using an algorithm-based diagnostic approach in the setting of a dedicated GPS/ inherited bone marrow failure syndrome (IBMFS) clinic. Seventy-two (50%) patients had IBMFS (telomere biology disorders-32,Fanconi anemia-18, Diamond Blackfan Anemia - 11, congenital neutropenia-5, Schwachman-Diamond Syndrome-5 and Bloom Syndrome-1), 27 (19%) had GPS with antecedent thrombocytopenia (RUNX1-FPD-15, ANKRD26-6, ETV6-2, GATA1-1, MPL-3), 28 (19%) had GPS without antecedent thrombocytopenia (GATA2 haploinsufficiency-16, DDX41-10, CBL-1 and CEBPA-1) and 17 (12%) had general cancer predisposition syndromes (ataxia telangiectasia-7, heterozygous ATM variants-3, CHEK2-2, TP53-2, CDK2NA-1, NF1-1 and Nijmegen Breakage Syndrome-1). Homozygous and heterozygous ATM pathogenic variants were exclusively associated with lymphoproliferative disorders (LPD), while DDX41 GPS was associated with LPD and myeloid neoplasms. The use of somatic NGS-testing identified clonal evolution in GPS patients, with ASXL1, RAS pathway genes, SRSF2 and TET2 being most frequently mutated. Fifty-two (91%) of 59 prospectively identified GPS patients had a change in their management approach, including additional GPS-related screening in 42 (71%), referral for allogenic HSCT workup and screening of related donors in 16 (27%), medication initiation and selection of specific conditioning regimens in 14 (24%), and genetic counseling with specific intent of fertility preservation and preconceptual counseling in 10 (17%) patients; highlighting the importance of dedicated GPS screening, detection and management programs for patients with hematological neoplasms.
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http://dx.doi.org/10.1002/ajh.26321DOI Listing
November 2021

De novo isolated myeloid sarcoma: comparative analysis of survival in 19 consecutive cases.

Br J Haematol 2021 Aug 3. Epub 2021 Aug 3.

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Institutional database search (1999-2020) for acute myeloid leukaemia (AML) identified 109 cases of myeloid sarcoma (MS), of which 19 were isolated and presented de novo. The latter displayed longer survival (median 78 months), compared to MS with synchronous intramedullary AML (n = 32; median 16 months) and de novo AML without MS (n = 729; median 22 months; P = 0·13). However, the difference in survival was no longer apparent after accounting for bone marrow cytogenetic risk status (P = 0·67). Treatment-induced MS tumour resolution was not affected by the presence of intramedullary disease (P = 0·61). The current study clarifies the prognosis of de novo isolated MS, in the context of AML.
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http://dx.doi.org/10.1111/bjh.17742DOI Listing
August 2021

Second Stem Cell Transplantation for Relapsed Refractory Light Chain (AL) Amyloidosis.

Transplant Cell Ther 2021 07 8;27(7):589.e1-589.e6. Epub 2021 Apr 8.

Division of Hematology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Autologous stem cell transplantation (ASCT) is an effective treatment modality in light chain (AL) amyloidosis but can be offered only to a subset of patients. The feasibility, benefit, and risks of second ASCT (ASCT2) have been rarely reported. The objective of this study was to assess the utility of ASCT2 in AL amyloidosis and to identify the target population with the greatest benefit. This retrospective study examined all AL patients who underwent ASCT2 for relapsed refractory disease between 2003 and 2020. Twenty-six patients were included. The use of ASCT2 has increased over time, from 2.5% of all ASCTs from 2003 to 2011 to 5% from 2012 to 2020 (P = .056). The median time between the first ASCT (ASCT1) and ASCT2 was 7.2 years (range, 0.6 to 17.7). Fifty-four percent of patients received at least one line of therapy between ASCTs. Second stem cell mobilization prior to ASCT2 was required in 42% of patients. Full-dose melphalan (200 mg/m) was given to 73% of patients. Two patients had failed to engraft by day 100 but eventually recovered to normal blood counts. Both had second stem cell mobilization prior to ASCT2 with prior melphalan exposure. Four patients (15%) died before day 100. Progression-free and overall survival were significantly longer from ASCT2 for those who had durable remission after ASCT1 (≥5 years) and for those who did not receive therapy between ASCTs. ASCT2 is feasible and can produce favorable outcomes, especially among those with durable response to ASCT1. ASCT2, if chosen, should preferably be performed after durable response to ASCT1 and at first progression.
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http://dx.doi.org/10.1016/j.jtct.2021.03.031DOI Listing
July 2021

Impact of Novel Targeted Therapies and Cytogenetic Risk Groups on Outcome After Allogeneic Transplantation for Adult ALL.

Transplant Cell Ther 2021 02 11;27(2):165.e1-165.e11. Epub 2020 Dec 11.

Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, Florida. Electronic address:

Novel high-risk groups have recently been identified in adult acute lymphoblastic leukemia (ALL), including Philadelphia-like, therapy-related, and measurable residual disease after induction therapy. Furthermore, modern targeted therapies have recently been incorporated into ALL management; rituximab for CD20-positive and blinatumomab for measurable residual disease after induction therapy or relapsed or refractory disease. Allogeneic hematopoietic cell transplantation (allo-HCT) is recommended as consolidation therapy for high-risk ALL; however, its relative benefit for these high-risk groups and after novel therapies is unclear. We performed an analysis of posttransplantation outcomes in a cohort of 261 consecutive patients who underwent allo-HCT for ALL at the 3-site Mayo Clinic Cancer Center (January 1, 2008-December 31, 2018). With a median (range) follow-up of 22.4 months (0.5-135.0), the 100-day and 5-year cumulative incidences of nonrelapse mortality rates were 6.5% and 26.7%, respectively. The 5-year cumulative incidences of relapse and death were 22.6% and 46.2%, respectively. The 1-year estimate of the composite endpoint of graft-versus-host disease/relapse-free survival was 39.3%. We observed no associations of novel high-risk groups or modern targeted therapies with overall survival, nonrelapse mortality, or relapse in multivariable analysis. An increased risk of relapse was observed with T-ALL (hazard ratio, 2.16; 95% confidence interval, 1.14-4.09; P = .02) and hypodiploidy/near-triploidy (hazard ratio, 2.84; 95% confidence interval, 1.06-7.62; P = .04). Our analysis suggests that novel high-risk groups derive a similar benefit from allo-HCT as traditional high-risk adult ALL and that novel targeted therapies do not seem to independently predict for posttransplantation outcomes. It also calls for further exploration of maintenance strategies after Allo-HCT to prevent relapse in high-risk subgroups.
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http://dx.doi.org/10.1016/j.jtct.2020.10.015DOI Listing
February 2021

Hypomagnesemia at the time of autologous stem cell transplantation for patients with diffuse large B-cell lymphoma is associated with an increased risk of failure.

Blood Cancer J 2021 03 26;11(3):65. Epub 2021 Mar 26.

Division of Hematology, Department of Medicine, Mayo Clinic Rochester, Rochester, MN, 55905, USA.

Magnesium is an essential element that is involved in critical metabolic pathways. A diet deficient in magnesium is associated with an increased risk of developing cancer. Few studies have reported whether a serum magnesium level below the reference range (RR) is associated with prognosis in patients with diffuse large B cell lymphoma (DLBCL). Using a retrospective approach in DLBCL patients undergoing autologous stem cell transplant (AHSCT), we evaluated the association of hypomagnesemia with survival. Totally, 581 patients eligible for AHSCT with a serum magnesium level during the immediate pre-transplant period were identified and 14.1% (82/581) had hypomagnesemia. Hypomagnesemia was associated with an inferior event-free (EFS) and overall survival (OS) compared to patients with a serum magnesium level within RR; median EFS: 3.9 years (95% CI: 1.63-8.98 years) versus 6.29 years (95% CI: 4.73-8.95 years) with HR 1.63 (95% CI: 1.09-2.43, p = 0.017) for EFS, and median OS: 7.3 years (95% CI: 2.91-upper limit not estimable) versus 9.7 years (95% CI: 6.92-12.3 years) with HR 1.90 (95% CI: 1.22-2.96, p = 0.005) for OS months 0-12, respectively. These findings suggest a potentially actionable prognostic factor for patients with DLBCL undergoing AHSCT.
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http://dx.doi.org/10.1038/s41408-021-00452-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998023PMC
March 2021

Mayo Clinic experience with 1123 adults with acute myeloid leukemia.

Blood Cancer J 2021 03 2;11(3):46. Epub 2021 Mar 2.

Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.

Between 2004 and 2017, a total of 1123 adult patients (median age 65 years; 61% males) with newly diagnosed acute myeloid leukemia (AML), not including acute promyelocytic leukemia, were seen at the Mayo Clinic. Treatment included intensive (n = 766) or lower intensity (n = 144) chemotherapy or supportive care (n = 213), with respective median survivals of 22, 9, and 2 months (p < 0.01). Intensive chemotherapy resulted in complete remission (CR) and CR with incomplete count recovery (CRi) rates of 44 and 33%, respectively, with no difference in survival outcome between the two (p = 0.4). Allogeneic hematopoietic stem cell transplant (AHSCT) was documented in 259 patients and provided the best survival rate (median 55 months; p < 0.01). After a median follow-up of 13 months, 841 (75%) deaths were recorded. Multivariate analysis identified age >60 years (HR 2.2, 1.9-2.6), adverse karyotype (HR 2.9, 1.9-4.9), intermediate-risk karyotype (HR 1.6, 1.02-2.6), post-myeloproliferative neoplasm AML (HR 1.9, 1.5-2.4), and other secondary AML (HR 1.3 (1.1-1.6) as risk factors for shortened survival. These risk factors retained their significance after inclusion of FLT3/NPM1 mutational status in 392 informative cases: FLT3+NPM1- (HR 2.8, 1.4-5.6), FLT3+/NPM+ (HR 2.6 (1.3-5.2), and FLT3-NPM1- (HR 1.8, 1.0-3.0).
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http://dx.doi.org/10.1038/s41408-021-00435-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925511PMC
March 2021

Use of sublingual tacrolimus in adults undergoing hematopoietic cell transplant: A pilot study.

J Oncol Pharm Pract 2021 Feb 16:1078155221995230. Epub 2021 Feb 16.

Division of Hematology and Bone Marrow Transplant, Mayo Clinic, Rochester, MN, USA.

Introduction: Orally administered tacrolimus is widely used in hematopoietic cell transplant patients, but multiple clinical situations may arise rendering oral administration infeasible. The undesirable sequelae of intravenous administration, including toxicity, challenges with administration and cost call for innovative solutions to conserve existing supply and optimize safety and efficacy of medication delivery. We sought to demonstrate feasibility of sublingual tacrolimus use and estimate a sublingual-to-oral (SL:PO) conversion ratio in the hematopoietic cell transplant setting.

Methods: Ten adults undergoing allogeneic hematopoietic cell transplant received tacrolimus 0.04 mg/kg/dose twice daily. Initial doses were given via sublingual route and a steady state trough level was collected after 4 consecutive doses. Participants were then switched to oral tacrolimus, the dose adjusted for a goal trough 8-12ng/mL, and another steady state trough was drawn. Total daily dose was divided by trough concentration for each route to determine the dosing ratio of SL:PO.

Results: Median trough level following sublingual administration was 11.3 ng/mL. Three of these were within goal, 3 were low (4.7-6.4 ng/mL) and 4 were elevated (15.9-18.6 ng/mL). Median SL:PO ratio was 1.02. In 5 participants the SL:PO ratio was <1 (range 0.57-0.94) and in 5 the ratio was ≥1 (range 1.10-1.92). No significant barriers or intolerance to sublingual tacrolimus use were noted.

Conclusions: Results demonstrate reliable absorption with sublingual tacrolimus use in patients undergoing hematopoietic cell transplant. Sublingual administration may allow for avoidance of the undesirable complications of IV tacrolimus, such as increased toxicities, required hospitalization for continuous infusion, risk of dose conversion and dilution errors and increased cost.Trial Registry name: Use of Sublingual Tacrolimus in Adult Blood and Marrow Transplant Patients, NCT04041219https://clinicaltrials.gov/ct2/show/NCT04041219?term=NCT04041219&draw=2&rank=1.
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http://dx.doi.org/10.1177/1078155221995230DOI Listing
February 2021

D-index as a marker of bloodstream infections in patients with allogeneic hematopoietic stem cell transplantation.

Transpl Infect Dis 2021 Aug 1;23(4):e13588. Epub 2021 Mar 1.

Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA.

Background: Neutropenia is a risk factor for development of infections; however, the direct effect of neutropenia on development of bloodstream infection (BSI) is not known. D-index, which is area between the neutrophil time curve and a neutrophil count of 0.5 × 10 /L, incorporates the combined effect of severity and duration of neutropenia. We aimed to evaluate whether D-index can be used as a marker for BSI in patients with allogeneic stem cell transplantation.

Method: We conducted a retrospective cohort study of patients undergoing allogeneic stem cell transplantation between January 1, 2005, and September 30, 2015. The primary outcome measure was the development of BSI within 30 days of transplantation.

Results: A total of 714 patients were included in the study of whom 101 developed BSI. Patients with BSI had a significantly higher median D-index value compared with patients who did not have BSI (4990 vs. 3570, P < .001). As a marker, the performance of the D-index was similar to that of the duration of profound neutropenia (P = .18) and significantly better than the total duration of neutropenia (P = .001).

Conclusion: The D-index performed better than the total duration of neutropenia as a marker for BSI in patients with allogeneic stem cell transplantation. There was no difference between D-index and, a more easily calculable indicator, duration of profound neutropenia.
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http://dx.doi.org/10.1111/tid.13588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364926PMC
August 2021

The Impact of Obesity on the Outcomes of Adult Patients with Acute Lymphoblastic Leukemia - A Single Center Retrospective Study.

Blood Lymphat Cancer 2021 22;11:1-9. Epub 2021 Jan 22.

Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, MN, USA.

Introduction: Obesity is a worldwide problem that is related to cardiac disease, thrombosis and cancer. However, little is known about the impact of obesity on the outcomes of adult acute lymphoblastic leukemia (ALL) patients.

Methods: We retrospectively evaluated a cohort of 154 newly diagnosed adult ALL patients between 1994 and 2011 at Mayo Clinic (Rochester). According to the World Health Organization (WHO) international BMI classification, patients were stratified as underweight, normal weight, overweight, and obese. For some analyses, patients were also stratified according to a two-sided non-obese or obese classification.

Results: The median follow-up time was 8.37 years. Obese patients were more likely to be women (p=0.024) and ≥60 years old (p=0.003). Five-year mortality rates were higher in obese patients than non-obese [HR 95% CI: 1.60 (1.03-2.50) p=0.035]. This was also the case in subgroup analysis among T-cell patients although the number of patients was small [HR 95% CI: 5.42 (1.84-15.98) p<0.001]. There was no difference in mortality among the B-cell patients. After adjusting for baseline variables, the difference in mortality remained in several models. There was no difference in EFS or cumulative incidence of relapse rates between obese and non-obese patients among the overall population.

Discussion: In conclusion, our study suggests that adult ALL patients with obesity have lower survival rates, especially in T-cell ALL.
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http://dx.doi.org/10.2147/BLCTT.S269748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837742PMC
January 2021

Epidemiology, Risk Factors, and Outcomes of Diffuse Alveolar Hemorrhage After Hematopoietic Stem Cell Transplantation.

Chest 2021 06 9;159(6):2325-2333. Epub 2021 Jan 9.

Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN. Electronic address:

Background: Diffuse alveolar hemorrhage (DAH) is an uncommon complication of hematopoietic stem cell transplantation (HCT) that carries high morbidity and mortality. Limited contemporary data are available regarding the incidence, outcomes, and risk factors for DAH.

Research Question: What are the incidence, outcomes, and risk factors for DAH developing after HCT?

Methods: This was a single-center retrospective cohort study of patients who underwent HCT between January 1, 2005, and December 31, 2016. The incidence and outcomes of DAH development were evaluated. A multivariate logistic regression model was used to analyze differences between survivors and nonsurvivors.

Results: Of 4,350 patients undergoing first-time HCT, DAH was diagnosed in 99 (2.3%). DAH was seen in 40 of 3,536 autologous HCT recipients (1.1%) and 59 of 814 allogeneic HCT recipients (7.2%). Mean age was 53 ± 13 years, and median time of DAH diagnosis was 126 days (interquartile range, 19-349 days) after HCT. In-hospital mortality and mortality 1 year after DAH diagnosis were 55.6% and 76.8%, respectively. DAH diagnosis more than 30 days after transplantation (OR, 7.06; 95% CI, 1.65-30.14), low platelet count (OR, 0.98; 95% CI, 0.96-1.0; P = .02), elevated international normalized ratio (INR; OR, 4.08; 95% CI, 0.64-25.88; P = .046) and need for invasive mechanical ventilation (OR, 8.18; 95% CI, 1.9-35.21) were associated with higher in-hospital mortality. Steroid treatment did not alter mortality (P = .80) or length of stay (P = .65). However, among those who received steroids, survival was higher in whose who received modest-dose steroids (< 250 mg methylprednisolone equivalent/d) compared with those who received high-dose steroids (≥ 250 mg methylprednisolone equivalent/d; OR, 0.21; 95% CI, 0.07-0.72).

Interpretation: The mortality of DAH after HCT remains high, and DAH can occur long after transplantation. Later development of DAH (>30 days after HCT), need for invasive mechanical ventilation, thrombocytopenia, and elevated INR are all associated with worse outcomes.
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http://dx.doi.org/10.1016/j.chest.2021.01.008DOI Listing
June 2021

Pseudo-Volkmann contracture as a complication of chronic graft-versus-host disease.

Dermatol Ther 2021 01 5;34(1):e14701. Epub 2021 Jan 5.

Department of Dermatology, Mayo Clinic, Rochester, Minnesota, USA.

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http://dx.doi.org/10.1111/dth.14701DOI Listing
January 2021

Biomarker-guided preemption of steroid-refractory graft-versus-host disease with α-1-antitrypsin.

Blood Adv 2020 12;4(24):6098-6105

Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.

Steroid-refractory (SR) acute graft-versus-host disease (GVHD) remains a major cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT), but its occurrence is not accurately predicted by pre-HCT clinical risk factors. The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm probability (MAP) identifies patients who are at high risk for developing SR GVHD as early as 7 days after HCT based on the extent of intestinal crypt damage as measured by the concentrations of 2 serum biomarkers, suppressor of tumorigenesis 2 and regenerating islet-derived 3α. We conducted a multicenter proof-of-concept "preemptive" treatment trial of α-1-antitrypsin (AAT), a serine protease inhibitor with demonstrated activity against GVHD, in patients at high risk for developing SR GVHD. Patients were eligible if they possessed a high-risk MAP on day 7 after HCT or, if initially low risk, became high risk on repeat testing at day 14. Thirty high-risk patients were treated with twice-weekly infusions of AAT for a total of 16 doses, and their outcomes were compared with 90 high-risk near-contemporaneous MAGIC control patients. AAT treatment was well tolerated with few toxicities, but it did not lower the incidence of SR GVHD compared with controls (20% vs 14%, P = .56). We conclude that real-time biomarker-based risk assignment is feasible early after allogeneic HCT but that this dose and schedule of AAT did not change the incidence of SR acute GVHD. This trial was registered at www.clinicaltrials.gov as #NCT03459040.
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http://dx.doi.org/10.1182/bloodadvances.2020003336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756981PMC
December 2020

Pretransplant Risk Factors Can Predict Development of Acute Respiratory Distress Syndrome after Hematopoietic Stem Cell Transplantation.

Ann Am Thorac Soc 2021 06;18(6):1004-1012

Department of Critical Care Medicine, Sichuan University West China Hospital, Chengdu, China.

Acute respiratory distress syndrome (ARDS) is a common complication after hematopoietic stem cell transplantation (HCT) and is a major contributor to nonrelapse mortality. To better understand pretransplant risk factors for developing ARDS after HCT. This is a single-center observational study comparing risk factors for ARDS development in 164 patients who went on to develop post-HCT ARDS compared with 492 patients who did not. The patients were matched 1 to 3 on age, sex, type of transplant (allogeneic vs. autologous), and underlying disease. Pertinent risk factors were analyzed separately in multivariable conditional logistic regression after adjustment for variables known to be associated with ARDS development. Patients with ARDS were more likely to have a lower pretransplant pulmonary function as measured by forced vital capacity (FVC) (odds ratio [OR], 0.54 [0.42-0.70] per liter increase in FVC;  < 0.001), forced expiratory volume in one second (FEV) (OR, 0.52 [0.38-0.71] per liter increase in FEV;  < 0.001) and diffusing capacity (OR, 0.92 [0.88-0.96] per ml/min/mm Hg increase in diffusing capacity;  < 0.001). Several laboratory indices were predictive of subsequent ARDS development including elevated AST (aspartate aminotransferase) (OR, 1.01 [1.00-1.01];  < 0.008), lower serum albumin (OR, 0.44 [0.30-0.66];  < 0.001), lower pretransplant hemoglobin (OR, 0.82 [0.73-0.92];  = 0.001), and lower leukocyte count (OR, 0.88 [0.79-0.99];  < 0.03). Patients who went on to develop ARDS were more likely to have been hospitalized in the year before the transplant (OR, 1.11 [1.04-1.20];  = 0.003), and required invasive or noninvasive ventilation during that hospitalization. Lastly, patients with ARDS were significantly more likely to have received carboplatin, thalidomide, methotrexate, and cisplatin than the non-ARDS control subjects. Several risk factors for developing ARDS after HCT are identifiable at the time of transplantation, well before the development of critical illness and ARDS. The identification of risk factors long before ARDS develops is relatively unique to the HCT population. Further work is needed to develop usable risk prediction tools in this setting.
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http://dx.doi.org/10.1513/AnnalsATS.202004-336OCDOI Listing
June 2021

Characteristics and Outcome of Periengraftment Respiratory Distress Syndrome after Autologous Hematopoietic Cell Transplant.

Ann Am Thorac Soc 2021 06;18(6):1013-1019

Multidisciplinary Epidemiology and Translational Research in Intensive Care (METRIC) Laboratory.

The periengraftment respiratory distress syndrome (PERDS) is an early important cause of morbidity following autologous hematopoietic cell transplantation (HCT). There are few contemporary data describing PERDS. To determine prevalence, risk factors, and outcomes of PERDS after autologous HCT. This was a historical cohort study of adults undergoing autologous HCT at Mayo Clinic, Rochester, Minnesota, between 2005 and 2016. PERDS was defined as ) respiratory failure requiring supplemental oxygen within 5 days on either side of the neutrophil engraftment date, ) new pulmonary opacities on chest imaging, and ) exclusion of an infectious or cardiac etiology to explain the clinical presentation. Of 3,473 patients undergoing autologous HCT, 167 (4.8%) developed PERDS. Radiographic changes preceded engraftment in 77% of cases. In a multivariable regression model, risk factors for PERDS included female sex (odds ratio [OR], 1.73;  = 0.001), the number of preengraftment platelet transfusions (OR, 1.22;  = 0.002), and more rapid engraftment (OR, 0.72 per day longer;  < 0.001). PERDS cases were more likely to be admitted to the intensive care unit (47.3% vs. 9.5%,  < 0.001) and require intubation (20.4% vs. 1.6%,  < 0.001). In an adjusted 100-day death analysis, those diagnosed with PERDS were more likely to die (hazard ratio, 3.1; 95% confidence interval, 1.5-6.2;  = 0.002). PERDS is a common complication of autologous HCT and is associated with increased mortality and healthcare use. Radiographic evidence of pulmonary involvement precedes hematopoietic recovery. A larger number of platelet transfusions and more rapid engraftment appear to increase risk for PERDS.
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http://dx.doi.org/10.1513/AnnalsATS.202008-1032OCDOI Listing
June 2021

Use of autologous stem cells cryopreserved for over 15 years in stem cell transplantation for multiple myeloma.

Bone Marrow Transplant 2021 04 11;56(4):978-979. Epub 2020 Nov 11.

Division of Hematology, Mayo Clinic, Rochester, MN, USA.

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http://dx.doi.org/10.1038/s41409-020-01131-7DOI Listing
April 2021

Risk of relapse in patients receiving azithromycin after allogeneic HSCT.

Bone Marrow Transplant 2021 04 31;56(4):960-962. Epub 2020 Oct 31.

Department of Hematology, Mayo Clinic, Rochester, MN, USA.

Following publication of the ALLOZITHRO trial, the FDA released a safety announcement warning that azithromycin should not be given long-term to prevent BOS in patients with a blood or lymph cancer who have undergone allogeneic HSCT. Our site typically initiated azithromycin when patients were diagnosed with BOS post-transplant rather than empirically as prevention. The purpose of our study was to discern whether the use of azithromycin at the time of diagnosis of BOS increased risk of disease relapse in patients who received an allogeneic HSCT for malignant disease. We retrospectively reviewed 432 patients in 3 cohorts: Cohort (1) patients who received greater than or equal to 2 weeks of azithromycin therapy (n = 98); Cohort (2) patients who received azithromycin therapy for less than 2 weeks (n = 63); and Cohort (3) patients who never received azithromycin therapy (n = 271). Neither patients in Cohort 1 (HR 0.44; 95% CI, 0.12-1.53, P = 0.19) nor Cohort 2 (HR 0.66; 95% CI, 0.2-2.19, P = 0.49) were associated with an increased risk of relapse when compared to those who had never received azithromycin. Our data indicate that the prolonged use of azithromycin after allogeneic HSCT is not associated with an increased rate of hematologic relapse.
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http://dx.doi.org/10.1038/s41409-020-01095-8DOI Listing
April 2021

Long-term Outcomes of Sequential Hematopoietic Stem Cell Transplantation and Kidney Transplantation: Single-center Experience.

Transplantation 2021 07;105(7):1615-1624

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.

Background: Experience with sequential hematopoietic stem cell transplant (HSCT) and kidney transplant (KT) is limited.

Methods: We conducted a retrospective observational study of adult patients who underwent both HSCT and KT at our center, with a median follow-up of 11 y.

Results: In our 54 patients cohort (94% autologous HSCT), 36 (67%) patients received HSCT first followed by KT, while 18 (33%) received KT before HSCT. In both groups, AL amyloidosis represented 50% of hematologic diagnosis. Only 4 patients expired due to hematologic disease relapse (2 patients in each group) and only 3 allografts were lost due to hematologic disease recurrence (HSCT first n = 1 and KT first n = 2). Overall 1, 5, and 10 y death-censored graft survival rates were 94%, 94%, and 94%, respectively, for the HSCT first group and 89%, 89%, and 75%, respectively, for the KT first group. Overall 1, 5, and 10 y patients survival rates were 100%, 97% and 90%, respectively, for the HSCT first group and 100%, 76%, and 63%, respectively, for the KT first group.

Conclusions: Our study supports safety of sequential KT and HSCT, with improved overall patient survival compared to recipients of HSCT remaining on dialysis and good long-term kidney allograft outcome.
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http://dx.doi.org/10.1097/TP.0000000000003477DOI Listing
July 2021

Chronic graft-versus-host disease in pancreas after kidney transplant recipients - An unrecognized entity.

Am J Transplant 2021 02 20;21(2):883-888. Epub 2020 Sep 20.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA.

Graft-versus-host disease (GVHD), a common complication after peripheral blood stem cell or bone marrow transplantation, rarely occurs in kidney and pancreas transplant recipients. The true incidence may be confounded by the rarity of the disorder, with a resultant lack of appreciation of the diagnosis as a potential cause of common clinical manifestations such as cytopenias and immune dysfunction. Reports of GVHD in kidney and pancreas transplant recipients almost uniformly describe patients in the early posttransplant period (days to months) with the typical manifestations of acute GVHD involving the skin, liver, and intestines. In contrast, reports of solid organ transplant recipients with clinical features more consistent with chronic GVHD (cGVHD) are lacking, raising concern of underrecognition of this severe complication. Occurrence later after transplant may be even more likely to result in lack of recognition. We report 2 cases of possible cGVHD occurring in recipients of pancreas after kidney transplantation, which were diagnosed at 5.5 and 42 months after pancreas transplant. Both patients presented with severe pancytopenia, multiple opportunistic infections, and features suggestive of cGVHD. Transplant professionals should be aware of the possibility of acute and cGVHD in pancreas after kidney transplant recipients and be able to recognize the clinical manifestations.
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http://dx.doi.org/10.1111/ajt.16273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870559PMC
February 2021

Leukocytosis and Tobacco Use: An Observational Study of Asymptomatic Leukocytosis.

Am J Med 2021 01 16;134(1):e31-e35. Epub 2020 Jul 16.

Division of Hematology.

Purpose: This study aimed to characterize the white blood cell differential of tobacco smoking-induced leukocytosis and describe the longitudinal impact of smoking cessation on this peripheral blood abnormality.

Methods: Medical records of patients undergoing evaluation by hematologists for persistent leukocytosis were reviewed. Patients in whom leukocytosis was determined to be secondary to tobacco use after exclusion of other causes were identified. Demographic and laboratory data were collected at time of diagnosis. Patients were longitudinally followed and information regarding smoking cessation and follow-up white blood cell values were recorded.

Results: Forty patients were determined to have smoking-induced leukocytosis. The median age was 49.5 years (range: 28-75 years), 24 patients were female, and the mean body mass index (BMI) was 31.5 kg/m. The mean white blood cell count was 13.3 × 10/L (range: 9.8-20.9 × 10/L); 39 patients had absolute neutrophilia (98%), 21 had lymphocytosis (53%), 20 had monocytosis (50%), and 19 had basophilia (48%). During follow-up, 11 patients either quit (n = 9) or reduced (n = 2) tobacco use. Reduction in tobacco smoking led to a significant decrease in mean white blood cell count (13.2 × 10/L vs 11.1 × 10/L, P = 0.02). The median time to decrease in white blood cell count following reduction in tobacco use was 8 weeks (range: 2-49 weeks).

Conclusions: Tobacco-induced leukocytosis was characterized by a mild elevation in total white blood cell count and was most commonly associated with neutrophilia, lymphocytosis, monocytosis, and basophilia. Cessation of smoking led to improvement in leukocytosis. Tobacco history should be elicited from all patients presenting with leukocytosis to limit unnecessary diagnostic testing, and counseling regarding smoking cessation should be offered.
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http://dx.doi.org/10.1016/j.amjmed.2020.06.014DOI Listing
January 2021

Incorporation of extracorporeal photopheresis into a reduced intensity conditioning regimen in myelodysplastic syndrome and aggressive lymphoma: results from ECOG 1402 and 1902.

Transfusion 2020 08 12;60(8):1867-1872. Epub 2020 Jul 12.

Genentech Inc, San Francisco, California.

Background: Extracorporeal photopheresis (ECP) is an immunomodulatory cellular therapy which has been shown to induce a tolerogenic state in patients with acute and chronic graft-vs-host disease. ECOG-ACRIN explored the activity of ECP as a part of a reduced intensity conditioning regimen in two multicenter trials in patients with MDS (E1902) and lymphomas (E1402). While both studies closed before completing accrual, we report results in 23 patients (17 MDS and 6 lymphoma).

Study Design And Methods: Patients received 2 days of ECP followed by pentostatin 4 mg/m2 /day for two consecutive days, followed by 600 cGy of total body irradiation prior to stem cell infusion. Immunosuppression for aGVHD was infusional cyclosporine A or tacrolimus and methotrexate on day +1, +3, with mycophenolate mofetil starting on day 100 for chronic GVHD prophylaxis.

Results: All patients engrafted, with median time to neutrophil and platelet engraftment of 15-18 days and 10-18 days respectively. Grade 3 or 4 aGVHD occurred in 13% and chronic extensive GVHD in 30%.

Conclusions: These studies demonstrate that ECP/pentostatin/TBI is well tolerated and associated with adequate engraftment of neutrophils and platelets in patients with lymphomas and MDS.
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http://dx.doi.org/10.1111/trf.15798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606221PMC
August 2020
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