Publications by authors named "Filippo Milano"

70 Publications

Planned granulocyte-colony stimulating factor adversely impacts survival after allogeneic hematopoietic cell transplantation performed with Thymoglobulin for myeloid malignancy.

Transplant Cell Ther 2021 Sep 7. Epub 2021 Sep 7.

Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.

Background: The in vivo depletion of recipient and donor T-lymphocytes using anti-thymocyte globulin (ATG) is widely adopted in allogeneic hematopoietic stem cell transplantation (HCT) to reduce the incidence of both graft failure and graft versus host disease (GVHD). However excess toxicity to donor lymphocytes may hamper immune reconstitution, compromising anti-tumour effects and increasing infection. Granulocyte-colony stimulating factor (G-CSF) administered early after HCT may increase ATG-mediated lympho-toxicity.

Objective: Our study objective was to investigate the effect of an interaction between ATG and post-transplant G-CSF on allogeneic transplant outcomes, using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry.

Study Design: We studied patients aged ≥18 years with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who received thymoglobulin-containing preparative regimens for HLA-matched sibling/unrelated or mismatched unrelated donor HCT from 2010-2018. The effect of planned G-CSF that was started between pre-transplant day 3 and post-transplant day 12 was studied in comparison to transplantations that did not include G-CSF. Cox regression models were built to identify risk factors associated with outcomes 1 year after transplantation.

Results: 874 patients met study eligibility criteria; 459 (53%) received planned G-CSF. HCTs with planned G-CSF significantly increased risk for non-relapse mortality (HR 2•03, p<0•0001; 21% vs. 12%) compared to HCTs without G-CSF. The 6-month incidence of viral infections was higher with G-CSF (56% vs. 47%, p=0•007), with a particular increase in EBV infections (19% vs. 11%, p=0•002). The observed higher non-relapse mortality with planned G-CSF led to lower overall survival (HR 1•52, p=0•0005; 61% vs. 72%). There was no difference in GVHD risk between treatment groups. We include two sub-group analyses showing our findings held true (i) in patients aged ≥50 years and (ii) in centers where G-CSF was used in some but not all patients.

Conclusion: In allogeneic peripheral blood HCT performed with Thymoglobulin for AML and MDS, G-CSF administered early post-transplant results in a two-fold increase in non-relapse mortality and a 10% absolute decrement in survival. The use of planned G-CSF in the early post-transplant period should be carefully considered on an individual patient basis, weighing any perceived benefits against these risks.
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http://dx.doi.org/10.1016/j.jtct.2021.08.031DOI Listing
September 2021

Comparison of haploidentical and umbilical cord blood transplantation after myeloablative conditioning.

Blood Adv 2021 Aug 30. Epub 2021 Aug 30.

University of Minnesota, Minneapolis, Minnesota, United States.

Haploidentical hematopoietic stem cell transplantation (haplo HSCT) has emerged as an important treatment modality. Most reports comparing haplo HSCT with post-transplant cyclophosphamide (PTCy) and other donor sources have focused on outcomes in older adults treated with reduced intensity conditioning. Therefore, in the current study, we evaluated outcomes in patients with hematological malignancy treated with myeloablative conditioning prior to haplo (n=375) or umbilical cord blood (UCB, n=333) HSCT. All haplo recipients received a 4 of 8 HLA matched graft while recipients of UCB were matched at 6-8/8 (n=145) or ≤5/8 (n=188) HLA antigens. Recipients of 6-8/8 UCB transplants were younger (14 years vs. 21 and 29 years) and more likely to have lower co-morbidity scores compared to recipients of ≤5/8 UCB and haplo HSCT (81% vs. 69% and 63%, respectively). UCB recipients were more likely to have acute lymphoblastic leukemia and transplanted in second complete remission (CR) whereas haplo HSCT recipients were more likely to have acute myeloid leukemia in first CR. Other characteristics, including cytogenetic risk were similar. Survival at 3 years was similar for the donor sources (66% haplo and 61% after ≤5/8 and 58% after 6-8/8 UCB). Notably, relapse at 3 years was lower in recipients of ≤5/8 UCB (21%, p=0.03) compared to haplo (36%) and 6-8/8 UCB (30%). However, non-relapse mortality was higher in ≤5/8 UCB (21%) compared to other groups (p<0.0001). These data suggest that haplo HSCT with PTCy after myeloablative conditioning provides an overall survival outcome comparable to that after UCB regardless HLA match group.
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http://dx.doi.org/10.1182/bloodadvances.2021004462DOI Listing
August 2021

Delayed-onset cytomegalovirus infection is frequent after discontinuing letermovir in cord blood transplant recipients.

Blood Adv 2021 08;5(16):3113-3119

Department of Medicine, University of Washington, Seattle, WA.

Cytomegalovirus (CMV)-seropositive umbilical cord blood transplantation (CBT) recipients have a high incidence of CMV-associated complications. There are limited data regarding the efficacy of letermovir for preventing clinically significant CMV infection (CS-CMVi), and the impact of letermovir prophylaxis on delayed-onset CMV reactivation after letermovir discontinuation, in CBT recipients. We compared the cumulative incidence of CS-CMVi and CMV detection in 21 CMV-seropositive CBT recipients receiving letermovir prophylaxis with a historical cohort of 40 CBT recipients receiving high-dose valacyclovir prophylaxis. Letermovir was administered on day +1 up to day +98. The cumulative incidence of CS-CMVi was significantly lower by day 98 in the letermovir cohort (19% vs 65%). This difference was lost by 1 year due to a higher incidence of delayed-onset CMV reactivation in the letermovir cohort. No patients developed CMV disease in the letermovir cohort within the first 98 days compared with 2 cases (2.4%) in the high-dose valacyclovir cohort; 2 patients developed CMV enteritis after discontinuing letermovir. Median viral loads were similar in both cohorts. Thus, letermovir is effective at preventing CS-CMVi after CBT, but frequent delayed-onset infections after letermovir discontinuation mandate close monitoring and consideration for extended prophylaxis.
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http://dx.doi.org/10.1182/bloodadvances.2021004362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405185PMC
August 2021

Frequent Eczematous Dermatitis in Unrelated Cord Blood Hematopoietic Cell Transplant Recipients Compared With Other Donor Types.

Transplant Cell Ther 2021 Jul 29. Epub 2021 Jul 29.

Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington, Seattle, Washington; Seattle Cancer Care Alliance, Seattle, Washington. Electronic address:

We have consistently noticed in our clinical practice eczematous dermatitis (EcD) without other pathologic findings of graft-versus-host disease (GVHD) in recipients of unrelated cord blood transplantation (CBT). We hypothesized that the incidence of EcD was higher in CBT compared with other donor types, and our objective in this study was to compare the frequency, clinical course, and response to therapy of EcD between CBT and non-CBT recipients. We conducted a retrospective study of 720 consecutive adult recipients of allogeneic hematopoietic cell transplants from 2010 to 2016 from any donor type and with follow-up for at least 1 year after transplantation. After using keyword-based automated scanning to identify "eczema," "dermatitis," or "spongiosis" terms in medical records, we retrieved 217 cases for manual record review. We identified 23 EcD cases (12 in CBT recipients and 11 in patients with other types of donors) with a median onset at 8 months after transplantation. The 2-year cumulative incidence of EcD was 20% (95% confidence interval [CI], 11.2% to 31.5%) after CBT and 1.7% (95% CI, .90% to 2.90%) with other types of donors (P < .0001). Fifteen cases had a skin biopsy without distinctive pathologic features of GVHD. The most common EcD-involved sites in CBT recipients were face (75%), neck (50%), and antecubital fossae (50%). Compared with patients with other types of donors, EcD after CBT was more likely to involve three or more sites (10 of 12 vs. 2 of 10; P = .008) and had a more protracted course (lasting >6 months in 6 of 58 vs. 1 of 661; P < .0001). In both groups, EcD responded to topical therapy, and only a few cases required systemic therapy. EcD is a relatively frequent skin condition among recipients of unrelated CBT. Irrespective of donor type, most cases of EcD can be successfully managed with only topical therapy. These findings will help providers recognize EcD, avoid potentially harmful systemic therapy, and better counsel transplant recipients.
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http://dx.doi.org/10.1016/j.jtct.2021.07.022DOI Listing
July 2021

Guidelines for the Prevention and Management of Graft-versus-Host Disease after Cord Blood Transplantation.

Transplant Cell Ther 2021 07;27(7):540-544

Hematologic Malignancies and Cellular Therapies, Department of Medicine, Duke Cancer Institute, Durham, North Carolina.

The incidence of graft-versus-host disease (GVHD) after cord blood (CB) transplantation (CBT) is lower than expected given the marked degree of human leukocyte antigen (HLA)-mismatch of CB grafts. While the exact mechanism that underlies this biology remains unclear, it is hypothesized to be due to the low number of mostly immature T-cells infused as part of the graft1,2, and increased tolerance of CB-derived lymphocytes induced by the state of pregnancy. Nevertheless, acute GVHD (aGVHD) is a significant complication of CBT. In contrast, the incidence of chronic GVHD (cGVHD) following CBT is lower than what is observed following matched related or unrelated donor HSC transplantation (HSCT)3-6. This review outlines the guidelines for the prevention and management of acute and chronic GVHD following CBT.
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http://dx.doi.org/10.1016/j.jtct.2021.03.012DOI Listing
July 2021

Parkinson's Disease Patient Monitoring: A Real-Time Tracking and Tremor Detection System Based on Magnetic Measurements.

Sensors (Basel) 2021 Jun 18;21(12). Epub 2021 Jun 18.

Department of Engineering, University of Perugia, 06125 Perugia, Italy.

Reliable diagnosis of early-stage Parkinson's disease is an important task, since it permits the administration of a timely treatment, slowing the progression of the disease. Together with non-motor symptoms, other important signs of disease can be retrieved from the measurement of the movement trajectory and from tremor appearances. To measure these signs, the paper proposes a magnetic tracking system able to collect information about translational and vibrational movements in a spatial cubic domain, using a low-cost, low-power and highly accurate solution. These features allow the usage of the proposed technology to realize a portable monitoring system, that may be operated at home or in general practices, enabling telemedicine and preventing saturation of large neurological centers. Validation is based on three tests: movement trajectory tracking, a rest tremor test and a finger tapping test. These tests are considered in the Unified Parkinson's Disease Rating Scale and are provided as case studies to prove the system's capabilities to track and detect tremor frequencies. In the case of the tapping test, a preliminary classification scheme is also proposed to discriminate between healthy and ill patients. No human patients are involved in the tests, and most cases are emulated by means of a robotic arm, suitably driven to perform required tasks. Tapping test results show a classification accuracy of about 93% using a k-NN classification algorithm, while imposed tremor frequencies have been correctly detected by the system in the other two tests.
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http://dx.doi.org/10.3390/s21124196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235095PMC
June 2021

Shared inflammatory pathways and therapeutic strategies in COVID-19 and cancer immunotherapy.

J Immunother Cancer 2021 05;9(5)

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

COVID-19, the syndrome caused by the infection with SARS-CoV-2 coronavirus, is characterized, in its severe form, by interstitial diffuse pneumonitis and acute respiratory distress syndrome (ARDS). ARDS and systemic manifestations of COVID-19 are mainly due to an exaggerated immune response triggered by the viral infection. Cytokine release syndrome (CRS), an inflammatory syndrome characterized by elevated levels of circulating cytokines, and endothelial dysfunction are systemic manifestations of COVID-19. CRS is also an adverse event of immunotherapy (IMTX), the treatment of diseases using drugs, cells, and antibodies to stimulate or suppress the immune system. Graft-versus-host disease complications after an allogeneic stem cell transplant, toxicity after the infusion of chimeric antigen receptor-T cell therapy and monoclonal antibodies can all lead to CRS. It is hypothesized that anti-inflammatory drugs used for treatment of CRS in IMTX may be useful in reducing the mortality in COVID-19, whereas IMTX itself may help in ameliorating effects of SARS-CoV-2 infection. In this paper, we focused on the potential shared mechanisms and differences between COVID-19 and IMTX-related toxicities. We performed a systematic review of the clinical trials testing anti-inflammatory therapies and of the data published from prospective trials. Preliminary evidence suggests there might be a benefit in targeting the cytokines involved in the pathogenesis of COVID-19, especially by inhibiting the interleukin-6 pathway. Many other approaches based on novel drugs and cell therapies are currently under investigation and may lead to a reduction in hospitalization and mortality due to COVID-19.
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http://dx.doi.org/10.1136/jitc-2021-002392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126446PMC
May 2021

Guidelines for Adult Patient Selection and Conditioning Regimens in Cord Blood Transplant Recipients with Hematologic Malignancies and Aplastic Anemia.

Transplant Cell Ther 2021 04;27(4):286-291

Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, Minnesota.

For cord blood transplantation (CBT), appropriate patient and conditioning regimen selection is necessary to achieve long-term disease-free survival. This review aims to provide comprehensive guidelines on these issues using evidence from the literature and experience at dedicated CBT centers. Topics include patient and disease characteristics that make CBT a good or poor choice and a review of outcomes in commonly used conditioning regimens in CBT. This is accompanied with recommendations on regimen intensity based on disease, organ function, and patient performance status and age. In addition, the use of antithymocyte globulin in CBT is discussed, as is the choice of conditioning in aplastic anemia patients who have access to acceptable CB units.
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http://dx.doi.org/10.1016/j.jtct.2020.11.008DOI Listing
April 2021

Alternative donor transplantation for myelodysplastic syndromes: haploidentical relative and matched unrelated donors.

Blood Adv 2021 02;5(4):975-983

Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI.

We compared outcomes in 603 patients with myelodysplastic syndrome (MDS) after HLA-haploidentical relative (n = 176) and HLA-matched unrelated (n = 427) donor hematopoietic cell transplantation (HCT) from 2012 to 2017, using the Center for International Blood and Marrow Transplant Research database. All transplantations used reduced-intensity conditioning regimens. Total-body irradiation plus cyclophosphamide and fludarabine was the predominant regimen for HLA-haploidentical relative donor HCT, and graft-versus-host disease (GVHD) prophylaxis was uniformly posttransplantation cyclophosphamide, calcineurin inhibitor, and mycophenolate. Fludarabine with busulfan or melphalan was the predominant regimen for HLA-matched unrelated donor HCT, and GVHD prophylaxis was calcineurin inhibitor with mycophenolate or methotrexate. Results of multivariate analysis revealed higher relapse (hazard ratio [HR], 1.56; P = .0055; 2-year relapse rate, 48% vs 33%) and lower disease-free survival (DFS) rates after HLA-haploidentical relative donor HCT (HR, 1.29; P = .042; 2-year DFS, 29% vs 36%). However, overall survival (OS) rates did not differ between donor type (HR, 0.94; P = .65; 2-year OS, 46% for HLA-haploidentical and 44% for HLA-matched unrelated donor HCT) because of mortality associated with chronic GVHD. Acute grade 2 to 4 GVHD (HR, 0.44; P < .0001) and chronic GVHD (HR, 0.36; P < .0001) were lower after HLA-haploidentical relative donor HCT. By 2 years, probability of death resulting from chronic GVHD was lower after HLA-haploidentical relative compared with HLA-matched unrelated donor HCT (6% vs 21%), negating any potential survival advantage from better relapse control. Both donor types extend access to transplantation for patients with MDS; strategies for better relapse control are desirable for HLA-haploidentical relative donor HCT, and effective GVHD prophylaxis regimens are needed for unrelated donor HCT.
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http://dx.doi.org/10.1182/bloodadvances.2020003654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903230PMC
February 2021

Polatuzumab Vedotin for Relapsed/Refractory Aggressive B-cell Lymphoma: A Multicenter Post-marketing Analysis.

Clin Lymphoma Myeloma Leuk 2021 03 18;21(3):170-175. Epub 2020 Dec 18.

Division of Medical Oncology, Department of Internal Medicine, University of Washington, Seattle, WA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Introduction: Polatuzumab vedotin is approved therapy in the United States for relapsed/refractory diffuse large B-cell lymphoma in combination with bendamustine and rituximab (Pola+BR). However, the safety and efficacy of Pola+BR outside of a clinical trial setting is unknown.

Patients And Methods: We analyzed use of pola-based therapy at 5 centers in the United States, including dose, response rates, progression-free survival (PFS), survival, and toxicity.

Results: Sixty-nine patients with aggressive B-cell lymphoma, including 66 with diffuse large B-cell lymphoma/high-grade B-cell lymphoma and 84% refractory to prior therapy, were treated. Responses occurred in of 50%, including 24% complete response. Median duration of response was 5.1 months, PFS was 2.0 months, and survival was 5.3 months, at 4 months median follow-up. Inferior PFS was associated with prior refractory disease (median, 57 days vs. not reached; P = .003) and lack of response to Pola+BR (PFS, 27 days vs. 152 days; P < .001). Discontinuation owing to planned cellular therapy was seen in 36% and owing to toxicity occurred in 12%; unplanned hospitalizations occurred in 36%.

Conclusions: We conclude that commercial Pola is applied to highly refractory lymphomas at our centers, often with intent to bridge to subsequent therapy. Although some clinical benefit was observed, efficacy was inferior to clinical trial data, especially among those with refractory disease.
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http://dx.doi.org/10.1016/j.clml.2020.12.013DOI Listing
March 2021

Pain Management in Childhood Leukemia: Diagnosis and Available Analgesic Treatments.

Cancers (Basel) 2020 Dec 7;12(12). Epub 2020 Dec 7.

Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.

Pain is one of the most common symptoms in children suffering from leukemia, who are often misdiagnosed with other childhood painful diseases such as juvenile idiopathic arthritis. Corticosteroid-induced osteonecrosis (ON) and vincristine-induced peripheral neuropathy (VIPN) are the most common painful manifestations. Additionally, ongoing pain may continue to impact quality of life in survivorship. This narrative review focuses on the pathophysiological mechanisms of pain in childhood leukemia and current available indications for analgesic treatments. Pain management in children is often inadequate because of difficulties in pain assessment, different indications across countries, and the lack of specific pediatric trials. Analgesic drugs are often prescribed off-label to children by extrapolating information from adult guidelines, with possible increased risk of adverse events. Optimal pain management should involve a multidisciplinary team to ensure assessment and interventions tailored to the individual patient.
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http://dx.doi.org/10.3390/cancers12123671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762342PMC
December 2020

Cord blood maternal microchimerism following unrelated cord blood transplantation.

Bone Marrow Transplant 2021 05 1;56(5):1090-1098. Epub 2020 Dec 1.

Clinical Research Division, Fred Hutchinson Cancer Research Center (FHCRC), Seattle, WA, USA.

Cord blood transplantation (CBT) is associated with low risk of leukemia relapse. Mechanisms underlying antileukemia benefit of CBT are not well understood, however a previous study strongly but indirectly implicated cells from the mother of the cord blood (CB) donor. A fetus acquires a small number of maternal cells referred to as maternal microchimerism (MMc) and MMc is sometimes detectable in CB. From a series of 95 patients who underwent double or single CBT at our center, we obtained or generated HLA-genotyping of CB mothers in 68. We employed a technique of highly sensitive HLA-specific quantitative-PCR assays targeting polymorphisms unique to the CB mother to assay CB-MMc in patients post-CBT. After additional exclusion criteria, CB-MMc was evaluated at multiple timepoints in 36 patients (529 specimens). CB-MMc was present in seven (19.4%) patients in bone marrow, peripheral blood, innate and adaptive immune cell subsets, and was detected up to 1-year post-CBT. Statistical trends to lower relapse, mortality, and treatment failure were observed for patients with vs. without CB-MMc post-CBT. Our study provides proof-of-concept that maternal cells of the CB graft can be tracked in recipients post-CBT, and underscore the importance of further investigating CB-MMc in sustained remission from leukemia following CBT.
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http://dx.doi.org/10.1038/s41409-020-01149-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119290PMC
May 2021

Factors associated with outcomes after a second CD19-targeted CAR T-cell infusion for refractory B-cell malignancies.

Blood 2021 01;137(3):323-335

Clinical Research Division and.

CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy has shown significant efficacy for relapsed or refractory (R/R) B-cell malignancies. Yet, CD19 CAR T cells fail to induce durable responses in most patients. Second infusions of CD19 CAR T cells (CART2) have been considered as a possible approach to improve outcomes. We analyzed data from 44 patients with R/R B-cell malignancies (acute lymphoblastic leukemia [ALL], n = 14; chronic lymphocytic leukemia [CLL], n = 9; non-Hodgkin lymphoma [NHL], n = 21) who received CART2 on a phase 1/2 trial (NCT01865617) at our institution. Despite a CART2 dose increase in 82% of patients, we observed a low incidence of severe toxicity after CART2 (grade ≥3 cytokine release syndrome, 9%; grade ≥3 neurotoxicity, 11%). After CART2, complete response (CR) was achieved in 22% of CLL, 19% of NHL, and 21% of ALL patients. The median durations of response after CART2 in CLL, NHL, and ALL patients were 33, 6, and 4 months, respectively. Addition of fludarabine to cyclophosphamide-based lymphodepletion before the first CAR T-cell infusion (CART1) and an increase in the CART2 dose compared with CART1 were independently associated with higher overall response rates and longer progression-free survival after CART2. We observed durable CAR T-cell persistence after CART2 in patients who received cyclophosphamide and fludarabine (Cy-Flu) lymphodepletion before CART1 and a higher CART2 compared with CART1 cell dose. The identification of 2 modifiable pretreatment factors independently associated with better outcomes after CART2 suggests strategies to improve in vivo CAR T-cell kinetics and responses after repeat CAR T-cell infusions, and has implications for the design of trials of novel CAR T-cell products after failure of prior CAR T-cell immunotherapies.
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http://dx.doi.org/10.1182/blood.2020006770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819764PMC
January 2021

Role of Human Bocavirus Respiratory Tract Infection in Hematopoietic Cell Transplant Recipients.

Clin Infect Dis 2020 Aug 9. Epub 2020 Aug 9.

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: Limited data exist regarding the impact of human bocavirus (BoV) in hematopoietic cell transplant (HCT) recipients.

Methods: In a longitudinal surveillance study among allogeneic HCT recipients, pre-HCT and weekly post-HCT nasal washes and symptom surveys were collected through day 100, then at least every 3 months through 1 year post-HCT at the Fred Hutch (2005-2010). Samples were tested by multiplex semi-quantitative PCR for 12 viruses. Plasma samples from BoV+ subjects were analyzed by PCR. Separately, we conducted a retrospective review of HCT recipients with BoV detected in lower respiratory tract specimens.

Results: Among 51 children and 420 adults in the prospective cohort, 21 distinct BoV respiratory tract infections (RTIs) were observed by 1 year post-HCT in 19 patients. Younger age and exposure to children were risk factors for BoV acquisition. Univariable models among patients with BoV RTI showed higher peak viral load in nasal samples (p=0.04) and presence of respiratory copathogens (p=0.03) were associated with presence of respiratory symptoms but BoV plasma detection was not. Only watery eyes and rhinorrhea were associated with BoV RTI in adjusted models. With additional chart review, we identified 6 HCT recipients with BoV detected in lower respiratory tract specimens [incidence rate of 0.4% (9/2509) per sample tested]. Although all cases presented with hypoxemia, 4 had respiratory copathogens or concomitant conditions that contributed to respiratory compromise.

Conclusions: BoV RTI is infrequent in transplant recipients and associated with mild symptoms. Our studies did not demonstrate convincing evidence that BoV is a serious respiratory pathogen.
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http://dx.doi.org/10.1093/cid/ciaa1149DOI Listing
August 2020

Guidelines for Cord Blood Unit Selection.

Biol Blood Marrow Transplant 2020 12 28;26(12):2190-2196. Epub 2020 Jul 28.

Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Optimal cord blood (CB) unit selection is critical to maximize the likelihood of successful engraftment and survival after CB transplantation (CBT). However, unit selection can be complex because multiple characteristics must be considered including unit cell dose, donor-recipient human leukocyte antigen (HLA) match, and unit quality. This review provides evidence-based and experience-based comprehensive guidelines for CB unit selection. Topics addressed include the use of both the TNC and the CD34 cell dose, as well as the CD34 cell to TNC content ratio to evaluate unit progenitor cell content and engraftment potential, the acceptable TNC and CD34 cell dose criteria that define an adequate single-unit graft, and the indication and acceptable cell dose criteria for double-unit grafts. The acceptable criteria for 6-loci (HLA-A, -B antigen, -DRB1 allele) and 8-allele (HLA-A, -B, -C, -DRB1) donor-recipient HLA match, the evaluation of patients with donor-specific HLA antibodies, and the multiple determinants of unit quality are also reviewed in detail. Finally, a practical step-by-step guide to CB searches and the principles that guide ultimate graft selection are outlined.
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http://dx.doi.org/10.1016/j.bbmt.2020.07.030DOI Listing
December 2020

Treosulfan-based conditioning is feasible and effective for cord blood recipients: a phase 2 multicenter study.

Blood Adv 2020 07;4(14):3302-3310

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Although the use of treosulfan (TREO) in conventional donor hematopoietic cell transplantation (HCT) has been extensively evaluated, its use in cord blood transplantation (CBT) for hematologic malignancies has not been reported. Between March 2009 and October 2019, 130 CBT recipients were enrolled in this prospective multicenter phase 2 study. The conditioning regimen consisted of TREO, fludarabine, and a single fraction of 2 Gy total-body irradiation. Cyclosporine and mycophenolate mofetil were used for graft-versus-host disease prophylaxis. The primary end point was incidence of graft failure (GF), and based on risk of GF, patients were classified as low risk (arm 1, n = 66) and high risk (arm 2, n = 64). The median age was 45 years (range, 0.6-65 years). Disease status included acute leukemias in first complete remission (CR; n = 56), in ≥2 CRs (n = 46), and myelodysplastic (n = 25) and myeloproliferative syndromes (n = 3). Thirty-five patients (27%) had received a prior HCT. One hundred twenty-three patients (95%) engrafted, with neutrophil recovery occurring at a median of 19 days for patients on arm 1 and 20 days for patients on arm 2. The 3-year overall survival, relapse-free survival (RFS), transplant-related mortality, and relapse for the combined groups were 66%, 57%, 18%, and 24%, respectively. Among patients who had a prior HCT, RFS at 3 years was 48%. No significant differences in clinical outcomes were seen between the 2 arms. Our results demonstrate that TREO-based conditioning for CBT recipients is safe and effective in promoting CB engraftment with favorable clinical outcomes. This trial was registered at www.clinicaltrials.gov as #NCT00796068.
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http://dx.doi.org/10.1182/bloodadvances.2020002222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391133PMC
July 2020

An evaluation of the objectivity and reproducibility of shear wave elastography in estimating the post-mortem interval: a tissue biomechanical perspective.

Int J Legal Med 2020 Sep 17;134(5):1939-1948. Epub 2020 Jul 17.

Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.

Cadaveric rigidity-also referred to as rigor mortis-is a valuable source of information for estimating the time of death, which is a fundamental and challenging task in forensic sciences. Despite its relevance, assessing the level of cadaveric rigidity still relies on qualitative and often subjective observations, and the development of a more quantitative approach is highly demanded. In this context, ultrasound shear wave elastography (US SWE) appears to be a particularly well-suited technique for grading cadaveric rigidity, as it allows non-invasive quantification of muscle stiffness in terms of Young's modulus (E), which is a widely used parameter in tissue biomechanics. In this pilot study, we measured, for the first time in the literature, changes in the mechanical response of muscular tissues from 0 to 60 h post-mortem (hpm) using SWE, with the aim of investigating its applicability to forensic practice. For this purpose, 26 corpses were included in the study, and the muscle mechanical response was measured at random times in the 0-60 hpm range. Despite the preliminary nature of this study, our data indicate a promising role of SWE in the quantitative determination of cadaveric rigidity, which is still currently based on qualitative and semiquantitative methods. A more in-depth study is required to confirm SWE applicability in this field in order to overcome some of the inherent limitations of the present work, such as the rather low number of cases and the non-systematic approach of the measurements.
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http://dx.doi.org/10.1007/s00414-020-02370-5DOI Listing
September 2020

Guidelines for Cord Blood Unit Thaw and Infusion.

Biol Blood Marrow Transplant 2020 10 27;26(10):1780-1783. Epub 2020 Jun 27.

Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

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http://dx.doi.org/10.1016/j.bbmt.2020.06.018DOI Listing
October 2020

Graft Cryopreservation Does Not Impact Overall Survival after Allogeneic Hematopoietic Cell Transplantation Using Post-Transplantation Cyclophosphamide for Graft-versus-Host Disease Prophylaxis.

Biol Blood Marrow Transplant 2020 07 10;26(7):1312-1317. Epub 2020 Apr 10.

Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; BMT and Cellular Therapy Program, Medical College of Wisconsin, Milwaukee, Wisconsin.

The COVID-19 pandemic has created significant barriers to timely donor evaluation, cell collection, and graft transport for allogeneic hematopoietic stem cell transplantation (allo-HCT). To ensure availability of donor cells on the scheduled date of infusion, many sites now collect cryopreserved grafts before the start of pretransplantation conditioning. Post-transplantation cyclophosphamide (ptCY) is an increasingly used approach for graft-versus-host disease (GVHD) prophylaxis, but the impact of graft cryopreservation on the outcomes of allo-HCT using ptCY is not known. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared the outcomes of HCT using cryopreserved versus fresh grafts in patients undergoing HCT for hematologic malignancy with ptCY. We analyzed 274 patients with hematologic malignancy undergoing allo-HCT between 2013 and 2018 with cryopreserved grafts and ptCY. Eighteen patients received bone marrow grafts and 256 received peripheral blood stem cell grafts. These patients were matched for age, graft type, disease risk index (DRI), and propensity score with 1080 patients who underwent allo-HCT with fresh grafts. The propensity score, which is an assessment of the likelihood of receiving a fresh graft versus a cryopreserved graft, was calculated using logistic regression to account for the following: disease histology, Karnofsky Performance Score (KPS), HCT Comorbidity Index, conditioning regimen intensity, donor type, and recipient race. The primary endpoint was overall survival (OS). Secondary endpoints included acute and chronic graft-versus-host disease (GVHD), non-relapse mortality (NRM), relapse/progression and disease-free survival (DFS). Because of multiple comparisons, only P values <.01 were considered statistically significant. The 2 cohorts (cryopreserved and fresh) were similar in terms of patient age, KPS, diagnosis, DRI, HCT-CI, donor/graft source, and conditioning intensity. One-year probabilities of OS were 71.1% (95% confidence interval [CI], 68.3% to 73.8%) with fresh grafts and 70.3% (95% CI, 64.6% to 75.7%) with cryopreserved grafts (P = .81). Corresponding probabilities of OS at 2 years were 60.6% (95% CI, 57.3% to 63.8%) and 58.7% (95% CI, 51.9% to 65.4%) (P = .62). In matched-pair regression analysis, graft cryopreservation was not associated with a significantly higher risk of mortality (hazard ratio [HR] for cryopreserved versus fresh, 1.05; 95% CI, .86 to 1.29; P = .60). Similarly, rates of neutrophil recovery (HR, .91; 95% CI, .80 to 1.02; P = .12), platelet recovery (HR, .88; 95% CI, .78 to 1.00; P = .05), grade III-IV acute GVHD (HR, .78; 95% CI, .50 to 1.22; P = .27), NRM (HR, 1.16; 95% CI, .86 to 1.55; P = .32) and relapse/progression (HR, 1.21; 95% CI, .97 to 1.50; P = .09) were similar with cryopreserved grafts versus fresh grafts. There were somewhat lower rates of chronic GVHD (HR, 78; 95% CI, .61 to .99; P = .04) and DFS (HR for treatment failure, 1.19; 95% CI, 1.01 to 1.29; P = .04) with graft cryopreservation that were of marginal statistical significance after adjusting for multiple comparisons. Overall, our data indicate that graft cryopreservation does not significantly delay hematopoietic recovery, increase the risk of acute GVHD or NRM, or decrease OS after allo-HCT using ptCY.
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http://dx.doi.org/10.1016/j.bbmt.2020.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194895PMC
July 2020

High Incidence of Herpes Zoster After Cord Blood Hematopoietic Cell Transplant Despite Longer Duration of Antiviral Prophylaxis.

Clin Infect Dis 2021 04;72(8):1350-1357

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Background: Cord blood transplant (CBT) recipients have a high incidence of herpes zoster (HZ) in the context of short-term peritransplant antiviral prophylaxis. In 2009, international guidelines recommended HZ prophylaxis for at least 1 year after hematopoietic cell transplant. The impact of longer-term antiviral prophylaxis on HZ incidence after CBT is unknown.

Methods: We retrospectively analyzed varicella zoster virus (VZV)-seropositive CBT recipients who were transplanted between 2006 and 2016. We abstracted HZ events and other variables for up to 5 years post-CBT. We calculated the cumulative incidence of HZ and used Cox proportional hazards regression to identify variables associated with HZ.

Results: The study cohort consisted of 227 patients. Among 1-year survivors, 91% were still receiving prophylaxis, for a median duration of 20.6 months. HZ occurred in 44 patients (19%) at a median of 23.6 months. The cumulative incidence of HZ by 1 year after CBT was 1.8% (95% confidence interval [CI], .1%-4%), but increased to 26% (95% CI, 19%-33%) by 5 years. In a multivariable analysis, acute graft-vs-host disease was associated with increased risk, whereas antiviral prophylaxis was associated with reduced risk for HZ (adjusted hazard ratio, 0.19 [95% CI, .09-.4]). There was no association between CD4+ T-cell counts at 1 year post-CBT and subsequent risk for HZ.

Conclusions: We found a high incidence of HZ after CBT despite antiviral prophylaxis for > 1 year. Based on these findings, we suggest longer duration of prophylaxis for HZ after CBT. Compliance with antiviral prophylaxis, VZV-specific immune monitoring, and vaccination to mitigate HZ after CBT also require further study.
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http://dx.doi.org/10.1093/cid/ciaa222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075034PMC
April 2021

Presentation of BK polyomavirus-associated hemorrhagic cystitis after allogeneic hematopoietic cell transplantation.

Blood Adv 2020 02;4(4):617-628

Fred Hutchinson Cancer Research Center, Seattle, WA.

BK polyomavirus (BKPyV) has been associated with hemorrhagic cystitis (HC) after allogeneic hematopoietic cell transplantation (HCT), but the natural history of HC and factors associated with the clinical course are incompletely understood. We retrospectively analyzed allogeneic HCT patients transplanted from 2007-2017 who presented after platelet engraftment or after day 28 post-HCT with BKPyV-associated HC (BKPyV-HC), which was defined as a positive urine BKPyV PCR, ≥1 plasma BKPyV viral load result, and macroscopic hematuria (Bedi grade ≥2). Factors associated with resolution of macroscopic hematuria and resolution of all cystitis symptoms within 90 days after HC diagnosis were investigated in multivariable models. In 128 patients with BKPyV-HC, the median times from diagnosis to resolution of all symptoms, macroscopic hematuria, and urinary clots (present in 55% [71/128]) were 24 days (15-44), 17 days (10-30), and 14 days (5-26), respectively. Ninety percent of patients had BKPyV viremia at the onset of HC with a median viral load of 1850 copies/mL (interquartile range, 240-8550). In multivariable models, high plasma viral load (≥10 000 copies/mL) and cytopenias at the beginning of BKPyV-HC were significantly associated with longer macroscopic hematuria and cystitis symptoms. Use of cidofovir was not associated with shorter duration of illness. In conclusion, BKPyV-HC after allogeneic HCT is characterized by prolonged and severe symptoms and requires improved management strategies. High-grade viremia and cytopenias were associated with a longer duration of BKPyV-associated HC. Accurate descriptions of disease and factors associated with prolonged recovery will inform end points of future clinical trials.
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http://dx.doi.org/10.1182/bloodadvances.2019000802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042995PMC
February 2020

Are we underutilizing bone marrow and cord blood? Review of their role and potential in the era of cellular therapies.

F1000Res 2020 17;9. Epub 2020 Jan 17.

Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle, WA, 98109, USA.

Since the first hematopoietic stem cell transplant, over a million transplants have been performed worldwide. In the last decade, the transplant field has witnessed a progressive decline in bone marrow and cord blood utilization and a parallel increase in peripheral blood as a source of stem cells. Herein, we review the use of bone marrow and cord blood in the hematopoietic stem cell transplant setting, and we describe the recent advances made in different medical fields using cells derived from cord blood and bone marrow.
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http://dx.doi.org/10.12688/f1000research.20605.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970216PMC
October 2020

Safety of allogeneic hematopoietic cell transplant in adults after CD19-targeted CAR T-cell therapy.

Blood Adv 2019 10;3(20):3062-3069

Clinical Research Division, Fred Hutch, Seattle, WA.

Allogeneic hematopoietic cell transplantation (allo-HCT) is offered to selected patients after chimeric antigen receptor-modified T-cell (CAR-T) therapy. Lymphodepleting chemotherapy and CAR-T therapy have immunosuppressive and immunomodulatory effects that could alter the safety profile of subsequent allo-HCT. We reviewed our experience with 32 adults (acute lymphoblastic leukemia [ALL], n = 19; B-cell non-Hodgkin lymphoma [NHL]/chronic lymphocytic leukemia [CLL], n = 13) who received an allo-HCT after CAR-T therapy, with a focus on posttransplant toxicities. Myeloablative conditioning (MAC) was used in 74% of ALL patients and 39% of NHL/CLL patients. The median time from CAR-T therapy to allo-HCT was 72 days in ALL patients and 122 days in NHL/CLL patients. Cumulative incidences of grade 3-4 acute graft-versus-host disease (GVHD) and chronic GVHD were 25% and 10%, respectively. All patients had neutrophil recovery (median, 18.5 days) and all but 3 had platelet recovery (median, 12 days). Twenty-two percent had viral or systemic fungal infection within 100 days after allo-HCT. The 100-day and 1-year cumulative incidences of NRM were 16% and 21%, respectively, for ALL patients and 15% and 33%, respectively, for NHL/CLL patients. In ALL patients, later utilization of allo-HCT after CAR-T therapy was associated with higher mortality. In NHL/CLL patients, MAC was associated with higher mortality. Toxicities did not exceed the expected incidences in this high-risk population.
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http://dx.doi.org/10.1182/bloodadvances.2019000593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849954PMC
October 2019

Incidence, Risk Factors, and Outcomes of Idiopathic Pneumonia Syndrome after Allogeneic Hematopoietic Cell Transplantation.

Biol Blood Marrow Transplant 2020 02 9;26(2):413-420. Epub 2019 Oct 9.

Division of Pulmonary, Critical Care, and Sleep Medicine, University of Washington Medical Center, Seattle, Washington; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Our current knowledge of idiopathic pneumonia syndrome (IPS) predates improved specificity in the diagnosis of IPS and advances in hematopoietic cell transplantation (HCT) and critical care practices. In this study, we describe and update the incidence, risk factors, and outcomes of IPS. We performed a retrospective cohort study of all adults who underwent allogeneic HCT at the Fred Hutchinson Cancer Research Center between 2006 and 2013 (n = 1829). IPS was defined using the National Heart, Lung, and Blood Institute consensus definition: multilobar airspace opacities on chest imaging, absence of lower respiratory tract infection, and hypoxemia. We described IPS incidence and mortality within 120 and 365 days after HCT. We examined conditioning intensity (nonmyeloablative versus myeloablative with high-dose total body irradiation [TBI] versus myeloablative with low-dose TBI) as an IPS risk factor in a time-to-event analysis using Cox models, controlled for age at transplant, HLA matching, stem cell source, and pretransplant Lung function Score (a combined measure of impairment in Forced Expiratory Volume in the first second (FEV) and Diffusion capacity for carbon monoxide (DLCO)). Among 1829 HCT recipients, 67 fulfilled IPS criteria within 120 days (3.7%). Individuals who developed IPS were more likely to be black/non-Hispanic versus other racial groups and have severe pulmonary impairment but were otherwise similar to participants without IPS. In adjusted models, myeloablative conditioning with high-dose TBI was associated with increased risk of IPS (hazard ratio, 2.5; 95% confidence interval, 1.2 to 5.2). Thirty-one patients (46.3%) with IPS died within the first 120 days of HCT and 47 patients (70.1%) died within 365 days of HCT. In contrast, among the 1762 patients who did not acquire IPS in the first 120 days, 204 (11.6%) died within 120 days of HCT and 510 (29.9%) died within 365 days of HCT. Our findings suggest that although the incidence of IPS may be declining, it remains associated with post-transplant mortality. Future study should focus on early detection and identifying pathologic mediators of IPS to facilitate timely, targeted therapies for those most susceptible to lung injury post-HCT.
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http://dx.doi.org/10.1016/j.bbmt.2019.09.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035790PMC
February 2020

Negative prognostic value of intra-ductal fat infiltrate in breast cancer.

Pathol Res Pract 2019 Nov 13;215(11):152634. Epub 2019 Sep 13.

Department of Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy; "Diagnostica Medica" and "Villa dei Platani", Avellino, Italy (Neuromed group), Italy.

Background: Recent studies showed a correlation between Body Mass Index and both breast cancer occurrence and progression. Nevertheless, no study reported an accurate evaluation of intra-ductal fat infiltrate. Therefore, the main aim of this study was to evaluate the putative association between intra-ductal fat infiltrate (IDFi) and breast cancer subtypes by using digital pathology.

Methods: We retrospectively collected 220 breast biopsies. Paraffin serial sections were used for haematoxylin and eosin staining and immunohistochemical evaluation of the following markers: estrogen receptor (ER), progesterone receptor (PR), Ki67 and c-erb2. Three haematoxylin and eosin sections for each paraffin block were digitalized. Digital slides were used to evaluate the areas of IDFi. Five randomized areas were evaluated for each slide. By using GraphPad software IDFi areas was correlated with a) breast cancer histotype, b) presence of microcalcifications and c) biomarkers expression.

Results: Breast biopsies were classified as follow: 20 normal breast, 50 benign lesions, and 150 malignant lesions (85 ductal in situ carcinomas; 65 ductal infiltrating carcinomas). Statistical analysis showed a significant increase of IDFi in malignant lesions as compared to both normal breast and benign lesions. We noted higher IDFi in breast ductal carcinomas as compared to lobular lesions. Significant differences were observed between breast lesions with microcalcifications respect to lesions without calcifications. Noteworthy, we also found a positive association between IDFi and the expression of both ER and Ki67.

Conclusion: Results of our study highlighted the possible role of fat in breast cancer progression suggesting a negative prognostic value of IDFi.
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http://dx.doi.org/10.1016/j.prp.2019.152634DOI Listing
November 2019

Atopic Eczema: Genetic Analysis of , , and in Mediterranean Populations.

Biomed Res Int 2019 4;2019:3457898. Epub 2019 Jun 4.

Department of Biomedicine and Prevention, Tor Vergata University, via Montpellier 1, 00133, Rome, Italy.

To date, the genes associated with susceptibility to Atopic Eczema (AE) are mainly implicated in immunity, inflammation, and maintenance of skin barrier. Little is known about the possible relationship between genes modulating Extra-Cellular Matrix (ECM) and AE etiopathogenesis. In this regard, the primary objective of the present study has been the investigation of susceptibility biomarkers localized within genes encoding collagen proteins. Several studies have shown that polymorphisms within the genes encoding such proteins may generate abnormal connective tissues, making them more susceptible to mechanical stress, loss of epidermal integrity, and aging. We therefore decided to investigate three polymorphisms located in , and as potential susceptibility biomarkers for AE in a cohort of 1470 subjects of Mediterranean origin. The genes of interest have been selected considering that the ECM and immune/inflammatory response are strongly dysregulated in AE and other complex disorders. The study confirmed that the susceptibility to AE depends on a complex interaction between latitude, geographical localization, and the differential distribution of genetic variants among populations exposed to similar environmental factors.
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http://dx.doi.org/10.1155/2019/3457898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582825PMC
January 2020

CD34 cell content of 126 341 cord blood units in the US inventory: implications for transplantation and banking.

Blood Adv 2019 04;3(8):1267-1271

National Marrow Donor Program, Minneapolis, MN.

CD34 cell dose is critical for cord blood (CB) engraftment. However, the CD34 content of the CB inventory in the United States is unknown. We examined the CD34 cell content of 126 341 red blood cell-depleted US units banked from January 2007 to September 2017 with a total nucleated cell (TNC) count of ≥90 × 10 and a cryovolume of 24-55 mL. Median pre-cryopreservation TNC content was 127 × 10 (interquartile range [IQR], 108-156 × 10); CD34 cell content was 44 × 10 (IQR, 29 to 67 × 10). The median CD34:TNC ratio was 0.34%. TNC and CD34 cell content correlation was weak ( = 0.24). Of 7125 units with TNCs of ≥210 × 10, only 47% had CD34 content of ≥100 × 10 However, some units had high CD34 content for a given TNC count. Only 4% of CB units were acceptable as single-unit grafts (TNCs, ≥2.5 × 10/kg; CD34 cells, ≥1.5 × 10/kg) for 70-kg patients; 22% of units were adequate for 70-kg patients using lower dose criteria (TNCs, ≥1.5 × 10/kg; CD34 cells, ≥1.0 × 10/kg) suitable for a double-unit graft. These findings highlight that units with the highest TNC dose may not have the highest CD34 dose, units with unexpectedly high CD34 content (a ratio of >1.0%) should be verified, and the US CB inventory of adequately sized single units for larger patients is small. They also support the ongoing use of double-unit grafts, a focus on banking high-dose units, and development of expansion technologies.
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http://dx.doi.org/10.1182/bloodadvances.2018029157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482363PMC
April 2019

The influence of stem cell source on transplant outcomes for pediatric patients with acute myeloid leukemia.

Blood Adv 2019 04;3(7):1118-1128

Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.

When hematopoietic stem cell transplant (HSCT) is necessary for children with acute myeloid leukemia (AML), there remains debate about the best stem cell source. Post-HSCT relapse is a common cause of mortality, and complications such as chronic graft versus host disease (cGVHD) are debilitating and life-threatening. To compare post-HSCT outcomes of different donor sources, we retrospectively analyzed consecutive transplants performed in several international centers from 2005 to 2015. A total of 317 patients were studied: 19% matched sibling donor (MSD), 23% matched unrelated donor (MUD), 39% umbilical cord blood (UCB), and 19% double UCB (dUCB) recipients. The median age at transplant was 10 years (range, 0.42-21 years), and median follow-up was 4.74 years (range, 4.02-5.39 years). Comparisons were made while controlling for patient, transplant, and disease characteristics. There were no differences in relapse, leukemia-free survival, or nonrelapse mortality. dUCB recipients had inferior survival compared with matched sibling recipients, but all other comparisons showed similar overall survival. Despite the majority of UCB transplants being HLA mismatched, the rates of cGVHD were low, especially compared with the well-matched MUD recipients (hazard ratio, 0.3; 95% confidence interval, 0.14-0.67; = .02). The composite measure of cGVHD and leukemia-free survival (cGVHD-LFS), which represents both the quality of life and risk for mortality, was significantly better in the UCB compared with the MUD recipients (HR, 0.56; 95% confidence interval, 0.34-1; = .03). In summary, the use of UCB is an excellent donor choice for pediatric patients with AML when a matched sibling cannot be identified.
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http://dx.doi.org/10.1182/bloodadvances.2018025908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457227PMC
April 2019

Improved Survival after Cord Blood Transplantation: Single-Center Experience in Pediatric Patients Over a 2-Decade Period.

Biol Blood Marrow Transplant 2019 04 13;25(4):e117-e118. Epub 2019 Feb 13.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington. Electronic address:

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http://dx.doi.org/10.1016/j.bbmt.2019.02.010DOI Listing
April 2019

Prognostic Performance of the Augmented Hematopoietic Cell Transplantation-Specific Comorbidity/Age Index in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation from Alternative Graft Sources.

Biol Blood Marrow Transplant 2019 05 28;25(5):1045-1052. Epub 2018 Nov 28.

Clinical Research Division, Fred Hutchinson Cancer Research Center; Seattle, Washington; Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine; Seattle, Washington. Electronic address:

The Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) was developed and validated to weigh the burden of pretransplantation comorbidities and estimate their impact on post-transplantation risks of nonrelapse mortality (NRM). Recently, the HCT-CI was augmented by the addition of both age and the values of 3 markers: ferritin, albumin, and platelet count. So far, research involving The HCT-CI has been limited almost exclusively to recipients of allogeneic hematopoietic cell transplantation (HCT) from HLA-matched grafts. To this end, we sought to investigate the discriminative capacity of an augmented comorbidity/age index among 724 recipients of allogeneic HCT from HLA-mismatched (n = 345), haploidentical (n = 117), and umbilical cord blood (UCB; n = 262) grafts between 2000 and 2013. In the overall cohort, the augmented comorbidity/age index had a higher c-statistic estimate for prediction of NRM compared with the original HCT-CI (.63 versus .59). Findings were similar for recipients of HLA-mismatched (.62 versus .59), haploidentical (.60 versus .54), or UCB grafts (.65 versus .61). Compared with patients with an HCT-CI score ≥4, those with a score <4 had a higher survival rate among recipients of HLA-mismatched (55% versus 39%; P < .0008), HLA-haploidentical (58% versus 38%; P = .01), or UCB (67% versus 48%; P = .004) grafts. Our results demonstrate the utility of the augmented comorbidity/age index as a valid prognostic tool among recipients of allogeneic HCT from alternative graft sources.
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http://dx.doi.org/10.1016/j.bbmt.2018.11.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511303PMC
May 2019
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