Genome editing in clinical practice: A model study for next-gen hematopoietic cell transplants in hematologic malignancies.
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ABSTRACT:
SUBMITTER: Derigs P
PROVIDER: S-EPMC10907159 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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Genome editing in clinical practice: A model study for next-gen hematopoietic cell transplants in hematologic malignancies.
Derigs Patrick P Müller-Tidow Carsten C
Molecular therapy. Methods & clinical development 20240226 1
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Project description:AbstractPatients undergoing hematopoietic cell transplantation (HCT) must cope with physical and psychological symptoms. Yet, studies examining pre-HCT coping are limited. We aimed to characterize pre-HCT coping, evaluate the association of coping with baseline quality of life (QOL) and psychological distress, and identify sociodemographic factors associated with pre-HCT coping. We conducted a cross-sectional analysis of baseline data from a multisite randomized supportive care intervention trial among patients with hematologic malignancies undergoing allogeneic or autologous HCT. We assessed patient-reported QOL, psychological distress, and coping within 72 hours of admission for HCT. We used the median split method to dichotomize coping and multivariate regression analyses to characterize the association of coping with psychological distress and QOL. Of patients awaiting HCT (n = 360; mean age, 55.4 years; 49.7% autologous), 43.5% were high users of approach-oriented coping, whereas 31.3% were high users of avoidant coping. Patients reported high use of emotional support (60.9%), acceptance (51.2%), self-blame (33%), and denial (31.3%). Older age (≥65 years) was associated with less frequent use of avoidant coping (odds ratio, 0.5; P = .01). Approach-oriented coping was associated with better pre-HCT QOL (Beta(B) = 6.7; P = .001), and lower depression (B = -1.1; P = .001) and anxiety (B = -0.9; P = .02) symptoms. Avoidant coping was associated with worse pre-HCT QOL (B = -13.3; P < .001) and symptoms of depression (B = 1.9; P < .001), anxiety (B = 3.1; P < .001), and posttraumatic stress disorder (B = 8.1; P < .001). Pre-HCT coping is strongly associated with psychological distress and QOL. These data support the need for interventions to address coping during HCT hospitalization. This clinical trial was registered at www.clinicaltrials.gov as #NCT03641378.
| S-EPMC10945147 | biostudies-literature
Project description: Not available
| S-EPMC10912849 | biostudies-literature
Project description:Purpose of reviewIncorporation of minimal residual disease (MRD) testing in acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) has transformed the landscape of hematopoietic cell transplantation (HCT). Pre-HCT MRD has allowed prognostication of HCT outcomes for high-risk leukemia patients, whereas the detection of post-HCT MRD has allowed for interventions to decrease relapse.Recent findingsIn this review, we emphasize studies from the past two decades that highlight the critical role of MRD in HCT in pediatric ALL and AML. Advances in MRD detection methodology, using next-generation sequencing, have improved the sensitivity of MRD testing allowing for more accurate predictions of HCT outcomes for patients with relapsed and refractory ALL and AML. In addition, novel pre-HCT therapies, especially immunotherapy in ALL, have dramatically increased the number of patients who achieve MRD-negative remissions pre-HCT, resulting in improved HCT outcomes. Post-HCT MRD remains a challenge and new therapeutic interventions are needed to reduce post-HCT relapse.SummaryAs immunotherapy increases pre-HCT MRD-negative remissions, and next-generation sequencing-MRD is incorporated to improve the sensitivity of MRD detection, future clinical studies will investigate less toxic HCT approaches to reduce long-term sequelae and to identify which patients may benefit most from early post-HCT intervention to reduce relapse.
| S-EPMC7461816 | biostudies-literature
Project description:Allogenic hematopoietic cell transplantation (HSCT) is typically the preferred curative therapy for adult patients with acute myeloid leukemia, but its use has been reduced as a consequence of limited donor availability in the form of either matched-related donors (MRD) or matched-unrelated donors (MUD). Alternative options such as unrelated umbilical cord blood (UCB) transplantation and haploidentical HSCT have been increasingly studied in the past few decades to overcome these obstacles. A human leukocyte antigen- (HLA-) haploidentical donor is a recipient's relative who shares an exact haplotype with the recipient but is mismatched for HLA genes on the unshared haplotype. These dissimilarities pose several challenges to the outcomes of the patient receiving such a type of HSCT, including higher rates of bidirectional alloreactivity and graft failure. In the past 5 years, however, several nonrandomized studies have shown promising results in terms of graft success and decreased rates of alloreactivity, in part due to newer grafting techniques and graft-versus-host disease (GVHD) prophylaxis. We present here a summary and review of the latest results of these studies as well as a brief discussion on the advantages and challenges of haploidentical HSCT.
| S-EPMC4789357 | biostudies-literature
Project description:Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk factors for PGF included recipient age <30, HLA mismatch, male recipients of female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning and cryopreservation. In bone marrow transplants, total nucleated cell doses ⩽2.4 × 10(8) per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post transplant may provide the rationale for an early request for additional hematopoietic stem cells.
| S-EPMC4527886 | biostudies-literature
Project description:Hematologic malignancies are a group of neoplastic conditions that can develop from any stage of the hematopoiesis cascade. Small non-coding microRNAs (miRNAs) play a crucial role in the post-transcriptional regulation of gene expression. Mounting evidence highlights the role of miRNAs in malignant hematopoiesis via the regulation of oncogenes and tumor suppressors involved in proliferation, differentiation, and cell death. In this review, we provide current knowledge about dysregulated miRNA expression in the pathogenesis of hematological malignancies. We summarize data about the clinical utility of aberrant miRNA expression profiles in hematologic cancer patients and their associations with diagnosis, prognosis, and the monitoring of treatment response. Moreover, we will discuss the emerging role of miRNAs in hematopoietic stem cell transplantation (HSCT), and severe post-HSCT complications, such as graft-versus-host disease (GvHD). The therapeutical potential of the miRNA-based approach in hemato-oncology will be outlined, including studies with specific antagomiRs, mimetics, and circular RNAs (circRNAs). Since hematologic malignancies represent a full spectrum of disorders with different treatment paradigms and prognoses, the potential use of miRNAs as novel diagnostic and prognostic biomarkers might lead to improvements, resulting in a more accurate diagnosis and better patient outcomes.
| S-EPMC10177548 | biostudies-literature
Project description:BackgroundIsavuconazole (ISA) is an attractive candidate for primary mold-active prophylaxis in high-risk patients with hematologic malignancies or hematopoietic cell transplant (HCT) recipients. However, data supporting the use of ISA for primary prophylaxis in these patients are lacking.MethodsWe conducted a retrospective review of breakthrough invasive fungal infections (bIFIs) among adult hematologic malignancy patients and HCT recipients who received ≥7 days of ISA primary prophylaxis between 1 September 2016 and 30 September 2018. The incidence of bIFIs in patients receiving ISA was compared to those receiving posaconazole (POS) and voriconazole (VOR) during the same time period.ResultsOne hundred forty-five patients received 197 courses of ISA prophylaxis. Twelve bIFIs (Aspergillus fumigatus [5], Aspergillus species [2], Mucorales [2], Fusarium species [2], and Candida glabrata [1]) occurred, representing 8.3% of patients and 6.1% of courses, after a median duration of 14 days of ISA prophylaxis. All bIFIs occurred during periods of neutropenia. Seven patients (58.3%) died within 42 days of onset of bIFI. In addition, bIFIs complicated 10.2% of ISA, 4.1% of POS, and 1.1% of VOR courses among patients with de novo or relapsed/refractory acute myeloid leukemia during the study period, with invasive pulmonary aspergillosis (IPA) complicating 6.8% of ISA, 1.3% of POS, and zero VOR courses.ConclusionsAlthough ISA has been approved for treatment of invasive Aspergillus and mucormycosis, we observed an increased rate of bIFI, notably IPA, using ISA for primary prophylaxis. These results support the need for further study to determine the role of ISA as primary prophylaxis.
| S-EPMC7931837 | biostudies-literature
Project description:Caregivers of patients with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT) must cope with substantial caregiving burden, high rates of psychological distress, and diminished quality of life (QOL). However, data describing coping strategies before HSCT and the association between coping, QOL, and psychological outcomes in this population are lacking. We conducted a secondary analysis of data collected during a multisite randomized clinical trial of a supportive care intervention in HSCT recipients and their caregivers. Caregivers completed the Brief COPE, Hospital Anxiety and Depression Scale, and the Caregiver Oncology Quality of Life Questionnaire to measure coping strategies, psychological distress, and QOL, respectively. We grouped coping into 2 higher-order domains: approach-oriented (ie, emotional support and active coping) and avoidant (ie, self-blame and denial). We used the median split method to describe the distribution of coping and multivariate linear regression models to assess the relationship between coping and caregiver outcomes. We enrolled 170 caregivers, with a median (range) age of 53 (47-64) years. Most were White (87%), non-Hispanic (96%), and female (77%). Approach-oriented coping was associated with less anxiety (β = -0.210, P = .003), depression symptoms (β = -0.160, P = .009), and better QOL (β = 0.526, P = .002). In contrast, avoidant coping was associated with more anxiety (β = 0.687, P<.001), depression symptoms (β = 0.579, P < .001), and worse QOL (β = -1.631, P < .001). Our findings suggest that coping is related to distress and QOL among caregivers of HSCT recipients even before transplant. Hence, caregivers of patients with hematologic malignancies undergoing HSCT may benefit from resources that facilitate adaptive coping with the demands of caregiving.
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Project description:In the USA and other western nations, respiratory syncytial virus is one of the most commonly encountered respiratory viruses among patients who have been diagnosed with a hematologic malignancy or who have undergone a stem cell transplant. Multiple studies have been performed to evaluate the complications associated with respiratory syncytial virus infections. Other studies have evaluated therapeutic agents and strategies in which these agents can be used. There have also been numerous reports of outbreaks in bone marrow transplant units and oncology wards, where infection control measures have been invaluable in controlling the spread of disease. However, despite these novel approaches, respiratory syncytial virus continues to be potentially fatal in immunocompromised populations. In this review, we discuss the incidence of respiratory syncytial viral infections, risk factors associated with progression from upper respiratory tract infection to lower respiratory tract infection, other complications and outcomes (including mortality), management strategies, and prevention strategies in patients with a hematologic malignancy and in hematopoietic cell transplant recipients.
| S-EPMC6601091 | biostudies-literature
Project description:Patient-reported outcomes among survivors of pediatric hematopoietic stem cell transplant (HSCT) are understudied. We compared symptom prevalence, health-related quality of life (HRQOL), and risk factors in adult survivors of childhood hematologic malignancies treated with HSCT to those treated with conventional therapy and noncancer controls. Survivors of childhood hematologic malignancies (HSCT N = 112 [70% allogeneic, 30% autologous]; conventionally treated N = 1106) and noncancer controls (N = 242) from the St. Jude Lifetime Cohort Study completed surveys assessing 10 symptom domains and SF-36 HRQOL summary scores. Chronic health conditions (CHCs) were validated by clinical assessment. Multivariable logistic regression reveals that compared with noncancer controls, HSCT survivors endorsed a significantly higher symptom prevalence in sensation (OR = 4.7, 95% confidence interval [CI], 2.6-8.4), motor/movement (OR = 4.3, 95% CI, 1.6-11.0), pulmonary (OR = 4.6, 95% CI, 1.8-11.8), and memory domains (OR = 4.8, 95% CI, 2.5-9.2), and poorer physical HRQOL (OR = 6.9, 95% CI, 2.8-17.0). HSCT and conventionally treated survivors had a similar prevalence of all symptom domains and HRQOL (all P > .05); however, HSCT survivors had a significantly higher cumulative prevalence for specific symptoms: double vision (P = .04), very dry eyes (P < .0001), and trouble seeing when wearing glasses (P < .0001). Occurrence of organ-specific CHCs, instead of transplant receipt, was significantly associated with a higher prevalence of all symptom domains (all P < .05) in adult survivors of childhood cancer, except for pain and anxiety domains. This study found that patient-reported outcomes were equally impaired between HSCT and conventionally treated survivors, but poorer in both groups compared with noncancer controls. Poor patient-reported outcomes in all survivors of childhood hematologic malignancies correlated with the presence of CHCs, whether treated with conventional therapy or HSCT.
| S-EPMC7243142 | biostudies-literature