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Advances in hematopoietic cell transplant for the treatment of hematologic malignancies.

ABSTRACT: PURPOSE OF REVIEW:Incorporation 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 FINDINGS:In 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. SUMMARY:As 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.

SUBMITTER: Taraseviciute A

PROVIDER: S-EPMC7461816 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Advances in hematopoietic cell transplant for the treatment of hematologic malignancies.

Taraseviciute Agne A Pulsipher Michael A MA

Current opinion in pediatrics 20190201 1

<h4>Purpose of review</h4>Incorporation 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.<h4>Recent findings</h4>In this review, we emphasize studies from the past two decades tha ...[more]

PMID: 30585866

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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.

Project description:BackgroundIn Pseudomonas aeruginosa, fluoroquinolone exposure promotes resistance to carbapenems through upregulation of efflux pumps and transcriptional downregulation of the porin OprD. Evidence of this effect among hematologic malignancy (HM) patients or hematopoietic cell transplant (HCT) recipients receiving fluoroquinolone prophylaxis for neutropenia is lacking.MethodsWe retrospectively evaluated episodes of P. aeruginosa bloodstream infections in HM patients or HCT recipients over a 7-year period at our institution. We determined the association of fluoroquinolone prophylaxis at the time of infection with meropenem susceptibility of P. aeruginosa breakthrough isolates and risk factors for meropenem nonsusceptibility. Whole-genome sequencing (WGS) and phenotypic assessments of meropenem efflux pump activity were performed on select isolates to determine the mechanisms of meropenem resistance.ResultsWe analyzed 55 episodes of P. aeruginosa bacteremia among 51 patients. Breakthrough bacteremia while on fluoroquinolone prophylaxis was associated with nonsusceptibility to meropenem, but not to antipseudomonal β-lactams or aminoglycosides. The receipt of fluoroquinolone prophylaxis was independently predictive of bacteremia with a meropenem-nonsusceptible isolate. All meropenem-nonsusceptible isolates analyzed by WGS contained oprD inactivating mutations, and all meropenem-nonsusceptible isolates tested demonstrated reductions in the meropenem minimum inhibitory concentration in the presence of an efflux pump inhibitor. A phylogenetic analysis based on WGS revealed several clusters of closely related isolates from different patients.ConclusionsFluoroquinolone prophylaxis in HM patients and HCT recipients is associated with breakthrough bacteremia with meropenem-nonsusceptible P. aeruginosa strains, likely due to both mutations increasing efflux pump activity and the epidemiology of P. aeruginosa bloodstream infections in our patient population.

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Advances in hematopoietic cell transplant for the treatment of hematologic malignancies.

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Advances in hematopoietic cell transplant for the treatment of hematologic malignancies.

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