Background
CD34+ stem cells serve as the primary graft source for allogeneic transplants, with a minimum of 2–4 × 106 cells/kg needed for engraftment. There are conflicting data on outcomes at high ...stem cell doses, with studies limited by few patients receiving doses far above the minimum target.
Study design and Methods
In this retrospective, single‐center study of patients with hematologic malignancies who underwent matched unrelated donor transplants, we assessed outcomes for engraftment, survival, relapse, and graft‐versus‐host disease (GVHD) for the highest CD34+ dose quintile (>13 × 106 cells/kg, n = 36) compared to the remaining patients (n = 139). Similar analysis was performed correlating T cell dose and outcomes.
Results
There was no difference between the groups in neutrophil engraftment, with a trend toward faster platelet engraftment. There was no significant difference in mortality (adjusted risk ratio aRR = 1.02, 95% confidence interval CI = 0.85–1.22), relapse (aRR = 1.10, 95% CI = 0.85–1.42), or overall survival by Kaplan–Meier analysis (p = .44). High CD34+ dose was not associated with higher incidence of acute GVHD (aRR = 0.99 grades II–IV, aRR = 1.18 grades III–IV) or chronic GVHD (aRR = 0.87 overall, RR = 1.21 severe). There was limited correlation between CD34+ and T cell dose (R2 = .073), and there was no significant difference in survival, relapse, or GVHD in the highest T cell dose quintile (n = 33) compared to the remaining quintiles (n = 132).
Discussion
We found no difference in survival, relapse, or GVHD incidence or severity in patients receiving CD34+ doses above prior cutoffs reported in the literature. These data do not support the routine use of graft CD34+ dose reduction.
Background
It is not clear if all Americans have benefitted equally from the availability of chimeric antigen receptor T‐cell (CART) therapy. We aimed to evaluate if demographic differences existed ...among adult patients who received CART therapy and to assess predictors of CART treatment outcomes.
Methods
Records of patients ≥18 years who received CART therapy for non‐Hodgkin’s lymphoma, acute lymphoblastic leukemia, and multiple myeloma in 2018 were evaluated in the National Inpatient Sample. Acute complications and inhospital mortality were compared between two groups of CART recipients: Whites and non‐Whites. Logistic regression analysis was used to evaluate the association between sociodemographic factors and inhospital mortality.
Results
Of 1275 CART recipients that met inclusion criteria, there were 40.4% of females, 66.9% of Whites, Blacks (4.2%), Hispanics (13.3%), Asians or Pacific Islanders (4.2%), and Native Americans (1.3%). Up to 96.8% of CART procedures were performed in urban teaching hospitals, and 85.3% of CART recipients lived in metropolitan counties. Non‐Whites, compared to Whites, were younger at the time of CART therapy (p < 0.001). The inhospital mortality rate was higher in non‐Whites, though not statistically significant (5.4% vs. 4.4%, p = 0.764). There were no differences in length of hospital stay, hospital charges, or rates of acute toxicities between the two race groups. We found no association between race and treatment outcomes. Gender, neurotoxicity, and Charlson Comorbidity Index were significant predictors of inhospital mortality.
Conclusions
CART therapy recipients in the United States were more likely to be Whites and more likely to be residents of metropolitan areas. These observed demographic differences were not associated with treatment outcomes or inhospital mortalities.
The first CART product was approved for commercial use in 2017, but it is not clear if all Americans have benefitted equally from the availability of CART therapies. In this retrospective study, we evaluated the demographic characteristics of CART therapy recipients for the year 2018. We found that racial minorities (especially Blacks) and people who live outside metropolitan areas were less likely to receive CART therapies.
•Cytogenetically cryptic PML::RARA fusions is an exceedingly rare phenomenon in acute promyelocytic leukemia•Multiple methodologies may be employed for detecting the cryptic PML::RARA ...fusion•Concurrent mutations can be identified in cases of acute promyelocytic leukemia with a cryptic PML::RARA fusion; however, a unifying genomic feature remains elusive•For cases with a high clinical suspicion of acute promyelocytic leukemia and no cytogenetic evidence of a PML::RARA fusion, complementary techniques should be employed for further analysis
Acute promyelocytic leukemia (APL) is a unique leukemia that is characterized by the PML::RARA fusion. This fusion is often detected by conventional karyotype and fluorescence in situ hybridization (FISH); however, rare cases are cryptic and require molecular techniques to identify the PML::RARA fusion. Furthermore, as the incidence of these cases is rare, analysis by a targeted next-generation sequencing (NGS) panel of myeloid associated genes has never been reported. Herein, a clinical APL case is reported where the PML::RARA fusion was detected only by reverse transcriptase-polymerase chain reaction (RT-PCR), thus underscoring the necessity of utilizing complementary techniques when suspicion for APL is present.
After more than a decade of preclinical and clinical development, therapeutic infusion of mesenchymal stromal cells is now a leading investigational strategy for the treatment of acute ...graft-versus-host disease (GVHD). While their clinical use continues to expand, it is still unknown which of their immunomodulatory properties contributes most to their therapeutic activity. Herein we describe the proposed mechanisms, focusing on the inhibitory activity of mesenchymal stromal cells (MSCs) at immunologic checkpoints. A deeper understanding of the mechanism of action will allow us to design more effective treatment strategies.
Chronic lymphocytic leukemia (CLL) is characterized by progressive accumulation of nonfunctional mature B cells in blood, bone marrow and lymphoid tissues. In the last decade, our understanding of ...CLL and consequently our diagnostic and therapeutic approaches have changed dramatically. Conventional fludarabine based chemotherapy has led to improved disease response and longer survival in young patients with CLL. However its application in elderly patients has been restricted by substantial myelosuppression and infection. Treatment of CLL is now moving towards targeted therapy. The success of new class of agents such as monoclonal antibodies, proteasome inhibitors and immunomodulatory derivatives has sparked further search for treatment agents with novel targets to inhibit. The B cell receptor activating pathway involving the Bruton's tyrosine kinase (BTK) is crucial in B cell production and maintenance and is an attractive therapeutic target. Ibrutinib is an oral covalent inhibitor of the BTK pathway that induces apoptosis of B cells. Early phase studies with Ibrutinib either as a single agent or in combination regimens have shown promising results with an excellent safety profile in patients with high-risk, refractory or relapsed CLL and elderly treatment-naïve patients. This review summarizes the current knowledge of Ibrutinib in the treatment of CLL.
Secondary analysis of large datasets has become a useful alternative to address research questions outside the reach of clinical trials. It is increasingly utilized in hematology and oncology. In ...this review, we provided an overview of some examples of commonly used large datasets in the USA and described common research themes that can be pursued using such a methodology. We selected a sample of 14 articles on adult hematologic malignancies published in 2015 and highlighted their contributions as well as limitations.
Abstract only
e19020
Background: Allogeneic stem cell transplantation (alloSCT) is increasingly being offered to older patients with acute myeloid leukemia (AML) due to availability of ...reduced-intensity conditioning regimens and better supportive care. Though studies have shown improving alloSCT survival outcomes in older age groups, it is still not known if older age confers higher mortality and morbidity during transplant hospitalization. We queried a national inpatient database to evaluate in-hospital mortality and resource utilization during alloSCT for AML in patients >70 years compared to a younger age group. Methods: We conducted a retrospective study of alloSCT for AML patients ≥ 18 years using the 2018 National Inpatient Sample database. Hospitalizations were selected using International Classification of Disease, tenth revision (ICD-10) codes. Demographics, comorbidities, transplant, and outcome variables were compared between a reference age group (18-70 years) and a comparator group (> 70 years). Study outcomes were in-hospital mortality, length of stay (LOS) and transplant complications. Regression models were fit to assess the association between predictors and outcomes. Results: During the study period, 2610 alloSCT met the inclusion criteria. This cohort consisted of 50% males and 77% Caucasians. Only 7% of these alloSCT were performed for patients > 70 years. Patients >70 yrs had a lower proportion of females compared to the reference age group (32% versus 52%, p<0.01). There were no significant differences in racial distribution, Charlson comorbidity index or median income between the 2 age groups. In-hospital mortality rates for the reference age group versus >70 years were 3% and 5% respectively (p=0.35). In a multivariable model, we found no association between age >70 years and in-hospital transplant mortality. Acute graft versus host disease was more frequent among the reference age group (14% versus 2%, p=0.04), but there were no differences in LOS or rates of graft failure, respiratory failure, sepsis, and acute renal failure between the 2 groups. Conclusions: Despite similar in-hospital transplant outcomes as their younger counterparts, patients >70 years comprised only a small proportion of alloSCT performed for AML in our study. Females were more disproportionately affected by this age disparity. More studies are necessary to identify barriers to alloSCT for older AML patients, more so for older females.
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