Publications by authors named "P Islam"

17 Publications

Female Sex is Associated with Improved Long-Term Survival Following Allogeneic Hematopoietic Stem Cell Transplant.

Transplant Cell Ther 2021 Jun 16. Epub 2021 Jun 16.

Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, NC. Electronic address:

Background: Life expectancy for long-term survivors of allogeneic hematopoietic stem cell transplant (alloHSCT), defined as those living ≥5 years post-transplant, is significantly lower compared to that of the age-matched general population despite a relatively low primary disease relapse rate >2 years post-transplant. Among several factors, patient sex is increasingly recognized as a prognostic indicator of long-term survival.

Objective: We examined the influence of patient sex and donor-recipient sex matching on overall survival in a landmark analysis of long-term survivors.

Study Design: Using our institutional database supplemented with individual patient record review, we retrospectively investigated the relative influence of recipient sex and donor-recipient sex matching on outcomes of long-term survivors receiving alloHSCT between 1994 - 2014.

Results: Over this 20-year period, 247 met inclusion criteria for analysis; males and females had similar demographic and treatment characteristics. However, significantly more deaths after the 5-year landmark occurred in male recipients. Interestingly, donor sex did not have a significant impact on overall survival in multivariate analysis, and differences in overall survival of donor-recipient sex pairs was driven by recipient sex. In addition to recipient sex, only cGVHD retained significance as a covariate with impact on overall survival in multivariate analysis. Men experienced slightly higher, but non-significant, rates and increased severity of cGVHD, and a greater percentage of cGVHD-related mortality as compared to females.

Conclusion: In this long-term survival analysis of alloHSCT adult patients, one of the only to include follow-up to 15 years, our results show that women survive significantly longer than men irrespective of their age at transplant. This outcome is independent of other common pre-transplant prognostic indicators such as donor sex or performance status at transplant. Inferior survival for males is consistent with survival outcomes described in transplant literature. Gathering evidence suggests a biologic basis for long-term sex-determined outcomes, possibly due to differing rates or severity of cGVHD or sustained alloimmune tolerance in females. Larger studies are warranted to validate these retrospective clinical results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtct.2021.06.012DOI Listing
June 2021

Decreased Mortality in 1-Year Survivors of Umbilical Cord Blood Transplant vs. Matched Related or Matched Unrelated Donor Transplant in Patients with Hematologic Malignancies.

Transplant Cell Ther 2021 May 12. Epub 2021 May 12.

Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University, Durham, North Carolina. Electronic address:

Allogeneic hematopoietic stem cell transplantation (HCT) has the potential to cure hematologic malignancies but is associated with significant morbidity and mortality. Although deaths during the first year after transplantation are often attributable to treatment toxicities and complications, death after the first year may be due to sequelae of accelerated aging caused by cellular senescence. Cytotoxic therapies and radiation used in cancer treatments and conditioning regimens for HCT can induce aging at the molecular level; HCT patients experience time-dependent effects, such as frailty and aging-associated diseases, more rapidly than people who have not been exposed to these treatments. Consistent with this, recipients of younger cells tend to have decreased markers of aging and improved survival, decreased graft-versus-host disease, and lower relapse rates. Given that umbilical cord blood (UCB) is the youngest donor source available, we studied the outcomes after the first year of UCB transplantation versus matched related donor (MRD) and matched unrelated donor (MUD) transplantation in patients with hematologic malignancies over a 20-year period. In this single-center, retrospective study, we examined the outcomes of all adult patients who underwent their first allogeneic HCT through the Duke Adult Bone Marrow Transplant program from January 1, 1996, to December 31, 2015, to allow for at least 3 years of follow-up. Patients were excluded if they died or were lost to follow-up before day 365 after HCT, received an allogeneic HCT for a disease other than a hematologic malignancy, or received cells from a haploidentical or mismatched adult donor. UCB recipients experienced a better unadjusted overall survival than MRD/MUD recipients (log rank P = .03, median overall survival: UCB not reached, MRD/MUD 7.4 years). After adjusting for selected covariates, UCB recipients who survived at least 1 year after HCT had a hazard of death that was 31% lower than that of MRD/MUD recipients (hazard ratio, 0.69; 95% confidence interval, 0.47-0.99; P = .049). This trend held true in a subset analysis of subjects with acute leukemia. UCB recipients also experienced lower rates of moderate or severe chronic graft-versus-host disease (GVHD) and nonrelapse mortality, and slower time to relapse. UCB and MRD/MUD recipients experienced similar rates of grade 2-4 acute GVHD, chronic GHVD, secondary malignancy, and subsequent allogeneic HCT. UCB is already widely used as a donor source in pediatric HCT; however, adult outcomes and adoption have historically lagged behind in comparison. Recent advancements in UCB transplantation such as the implementation of lower-intensity conditioning regimens, double unit transplants, and ex vivo expansion have improved early mortality, making UCB an increasingly attractive donor source for adults; furthermore, our findings suggest that UCB may actually be a preferred donor source for mitigating late effects of HCT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jtct.2021.05.002DOI Listing
May 2021

Controlled Transport of Stored Light.

Phys Rev Lett 2020 Oct;125(15):150501

Institut für Physik, Johannes Gutenberg-Universität Mainz, 55122 Mainz, Germany.

Controlled manipulation, storage, and retrieval of quantum information is essential for quantum communication and computing. Quantum memories for light, realized with cold atomic samples as the storage medium, are prominent for their high storage efficiencies and lifetime. We demonstrate the controlled transport of stored light over 1.2 mm in such a storage system and show that the transport process and its dynamics only have a minor effect on the coherence of the storage. Extending the presented concept to longer transport distances and augmenting the number of storage sections will allow for the development of novel quantum devices such as optical racetrack memories or optical quantum registers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1103/PhysRevLett.125.150501DOI Listing
October 2020

Establishment and maintenance of motor neuron identity via temporal modularity in terminal selector function.

Elife 2020 10 1;9. Epub 2020 Oct 1.

Department of Neurobiology, University of Chicago, Chicago, United States.

Terminal selectors are transcription factors (TFs) that establish during development and maintain throughout life post-mitotic neuronal identity. We previously showed that UNC-3/Ebf, the terminal selector of cholinergic motor neurons (MNs), acts indirectly to prevent alternative neuronal identities (Feng et al., 2020). Here, we globally identify the direct targets of UNC-3. Unexpectedly, we find that the suite of UNC-3 targets in MNs is modified across different life stages, revealing 'temporal modularity' in terminal selector function. In all larval and adult stages examined, UNC-3 is required for continuous expression of various protein classes (e.g. receptors, transporters) critical for MN function. However, only in late larvae and adults, UNC-3 is required to maintain expression of MN-specific TFs. Minimal disruption of UNC-3's temporal modularity via genome engineering affects locomotion. Another terminal selector (UNC-30/Pitx) also exhibits temporal modularity, supporting the potential generality of this mechanism for the control of neuronal identity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.59464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529460PMC
October 2020

Utilizing Real-World Evidence (RWE) to Improve Care in Chronic Lymphocytic Leukemia: Challenges and Opportunities.

Curr Hematol Malig Rep 2020 08;15(4):254-260

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Purpose Of Review: This review discusses important findings from real-world evidence (RWE) studies impacting the field of chronic lymphocytic leukemia (CLL), from prognostication to long-term management and sequencing of novel agents.

Recent Findings: RWE data, which represents a heterogeneous cohort of patients treated at non-academic centers and off-clinical trial, demonstrate several key differences between findings in randomized controlled trials (RCT) of novel agents in CLL. While toxicity and discontinuation rates are higher, survival outcomes are encouraging in clinical practice, with often equivalent outcomes from reduced-dose or time-limited therapy of drug. Though sequencing of novel agents lacks robust RCT data, RWE data provide important guidance for selection and sequencing of novel agents. RWE has critically informed our practice by providing diverse patient data and real-time analysis for important clinical questions outpacing the rapidly growing field of CLL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11899-020-00584-3DOI Listing
August 2020