Setting Of Stem Cell Transplantation Research Articles

Evaluating Risk Factors and Outcomes For Clostridium Difficile Infection (CDI) In Stem Cell Transplant (SCT) Recipients

IntroductionClostridium difficile infections (CDI) are the leading cause of infectious diarrhea among pts undergoing stem cell transplantation (SCT). Data from large pt samples evaluating the trends, risk factors, hospitalization outcomes are lacking. We have analyzed the Nationwide Inpt Sample (NIS) database to evaluate the trends in the incidence and the impact of CDI on hospitalization outcomes among SCT recipients. MethodsWe used the NIS database to obtain the hospitalization data for primary procedures of autologous and allogeneic SCT between 01/2001 until 12/2010. We performed separate multivariate logistic regression analyses to evaluate risk factors of CDI in SCT pts and hospitalization outcomes including length of stay (LOS), in-hospital mortality (IHM) and hospitalization charges. Comorbidites were identified using software that created measures reported by Elixhauser et al. ResultsThe incidence of CDI among transplant pts has remained relatively stable over time (Fig 1), with a higher cumulative incidence of CDI among recipients of allogeneic grafts (allogeneic vs. autologous SCT: 8.29% vs. 5.63%; p<0.001). There was an association between CDI and the presence of multiple comorbidities among autologous SCT pts (p=0.05), and a similar trend was seen in allogeneic transplant pts. Mean LOS (CDI vs. none: autologous 26 vs. 20 days, p<0.0001; allogeneic 42 vs 30 days, p<0.001; respectively), IHM (CDI vs. none: autologous, 4.0 vs. 2.2%, p=0.0003; allogeneic 12.7 vs 9.2%, p=0.0008) and mean hospitalization charges (CDI vs. none: autologous $208,025 vs. $145,250, p<0.0001; allogeneic $367,415 vs $270,366 p<0.0001; respectively) were significantly higher among SCT pts with CDI (Table 1). [Display omitted] Table 1Pt characteristics, multivariate regression models for evaluating risk and outcomes of SCT pts with CDIAutologous SCTAllogeneic SCTCDI (%) (N=3772)SCT patients (%) (N=63202)p-valueCDI (%) (N=3440)SCT patients (N=38066)p-valueMean age (SE)54.3 (0.52)52.02 (0.27)<0.000145.07 (0.64)46.57 (0.38)<0.0098Male2311 (61.3)37038 (58.6)0.15962188 (63.6)21906 (57.6)0.0005White2369 (77.4)26124 (74.3)0.10892199 (77.7)23695 (78)0.847Comorbidities ≥12945 (78)46872 (74.2)0.052607 (75.8)27712 (72.8)0.1073Medicare945 (25.1)12460 (19.8)<0.0001310 (9.0)4111 (10.8)0.183Medicaid330 (8.8)6818 (10.8)0.1161474 (13.8)3996 (10.5)0.0126Private Insurance2320 (61.6)40209 (63.8)0.24832486 (72.4)27601 (72.7)0.8798Mean LOS (SE)*26 (0.71)20 (0.27)<0.0001*42 (1.59)30 (0.68)<0.0001*IHM152 (4.0)1330 (2.1)0.0003438 (12.7)3360 (8.8)0.0008Charge Mean (SE)208025 (8370.6)145250 (4311.3)<0.0001*$367415 (15033)$270366 (11835)<0.0001*Multivariate logistic regression model evaluating risk of CDI in SCT patientsVariableOdds RatioRefp-valueOdds RatioRefp-value≥651.4 (0.987-1.985)Age <40 (Ref)0.19450.637 (0.426-0.953)0.0834Male1.25 (1.054-1.483)Female (Ref)0.01031.351 (1.157-1.576)Female (Ref)0.0001Medicare1.149 (0.878-1.502)Private (Ref)0.04390.85 (0.581-1.244)Private (Ref)0.4605Medicaid0.887 (0.642-1.226)0.76731.269 (0.920-1.749)0.0272No Comorbidities0.831 (0.650-1.063)Comorbidities ≥10.14060.829 (0.672-1.024)Comorbidities ≥10.082 ConclusionsThe incidence of CDI among both autologous and allogeneic SCTs have remained stable over the last decade, with a slightly higher risk among allogeneic SCT pts. CDI was associated with longer hospital stay, higher charges and higher IHM for both autologous and allogeneic transplant pts. While this analysis does not permit us to directly ascribe differences in outcome to CDI alone, these data suggest that CDI has a major morbid impact in the setting of SCT, and provides a rationale for development of more effective approaches for prevention of CDI in these pt populations. Disclosures:Kaufman:Onyx: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy; Millenium: Consultancy; Merck: Research Funding. Lonial:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Onyx: Consultancy.Multivariate logistic regression model evaluating hospitalization outcomes in SCT patients with CDI #CDIAbsencePresencep-valueCDIAbsencePresencep-valueLOS >19 days0.382 (0.31-0.466)1.00 (Ref)<0.0001LOS > 27 days0.337 (0.27-0.42)1.00 (Ref)<0.0001Charge > $125,0910.483 (0.40-0.58)<0.0001Charge > $22,60110.487 (0.38-0.67)<0.0001IHM0.68 (0.44-1.06)0.089IHM0.661 (0.50-0.87)0.0037SE: Standard error; *adjusted for age, race, sex, comorbidity and payer status.#Median LOS and charges used as cut-off for hospitalization outcomes

Spotlight on Melphalan Flufenamide: An Up-and-Coming Therapy for the Treatment of Myeloma.

Despite recent therapeutic advances, multiple myeloma (MM) patients experience relapses as they become resistant to various classes and combinations of treatment. Melphalan (L-PAM) is an ageless drug. However, its use in the autologous stem cell transplantation (ASCT) setting and the innovative quadruplet regimen as well as daratumumab, bortezomib, and prednisone make this old drug current yet. Melflufen is a peptide-conjugated alkylator belonging to a novel class of compounds, representing an overcoming of L-PAM in terms of mechanism of action and effectiveness. The improved melflufen cytotoxicity is related to aminopeptidase activity, notably present in normal and neoplastic cells and remarkably heavily overexpressed in MM cells. Upon entering a cell, melflufen is cleaved by aminopeptidases, ultimately releasing the L-PAM payload and eliciting further the inflow and cleavage of the conjugated peptide. This virtuous loop persists until all extracellular melflufen has been utilized. The aminopeptidase-driven accumulation results in a 50-fold increase in L-PAM cell enrichment as compared with free alkylator. This condition produces selective cytotoxicity, increased on-target cell potency, and decreased off-target cell toxicity, ultimately overcoming resistance pathways triggered by previous treatments, including alkylators. Due to its distinct mechanism of action, melflufen plus dexamethasone as a doublet, and in combination with other novel drugs, has the potential to be beneficial for a broad range of patients with relapsed/refractory (RR) MM in third- or even in second-line therapy. The safety profile of melflufen has been consistent across studies, and no new safety concerns have been identified when melflufen was administered in doublet and triplet combinations. Based on growing clinical evidence, melflufen could be not only a good addition in the fight against RRMM but also a drug with a very favorable tolerability profile.

Recognizing the Existence of Heparin Induced Thrombocytopenia and Thrombosis in the Setting of High-Dose Melphalan and Autologous Stem Cell Transplantation: A Single Institution Case Series

Background: Heparin induced thrombocytopenia and thrombosis (HIT/HITT) is a disorder characterized by transient hypercoagulability, with increased risk of venous or arterial thrombosis, related to the development of antibodies directed against the heparin-PF4 complex. HIT can occur in any patient receiving heparin but has rarely been described in the setting of high dose melphalan and autologous stem cell transplantation (HDM/SCT) so the true incidence in this population is unknown. Clinical suspicion of HIT in this setting is often clouded by the increased frequency of thrombocytopenia due to stem cell collection or high dose chemotherapy, as well as the increased risk of thrombosis in hematologic malignancies. We report five such cases, with clinically apparent and laboratory confirmed HIT that were diagnosed while undergoing treatment with high dose melphalan and autologous stem cell transplantation.Results: Five patients pursuing treatment with HDM/SCT were diagnosed with HIT during a five year period at our institution. Four patients were being treated for AL amyloidosis and one for multiple myeloma. The average patient age was 64 years (range, 59 to 69), including four males and 1 female. At the time of HIT diagnosis one patient was receiving prophylactic doses of enoxaparin due to a history of line-associated deep vein thrombosis. The other four patients had only been exposed to heparin as part of standard practice for central line placement, line flushes, or stem cell collection. Suspicion of HIT arose in all cases when the patient had delayed platelet recovery during the days following stem cell collection. Only one patient had proceeded with melphalan treatment before HIT was diagnosed. The average platelet nadir was 29, with a range of 6 to 68 x 109/L (Table 1). In two patients the development of thrombosis prompted the work-up for HIT: one with an internal jugular thrombosis and the other with limb threatening aortoiliac thrombosis requiring aortoiliac and femoral artery embolectomy with fasciotomy. All five patients had confirmation of diagnosis with heparin-PF4 antibody (optical density range, 0.5 to 3.3) and a positive serotonin release assay (SRA). Four patients were started on anticoagulation with fondaparinux or argatroban with appropriate platelet recovery in all patients. Three patients proceeded with HDM/SCT, while the remaining two patients received alternative therapies because the previously collected stem cells had been processed with heparin and could not be given to the patients.Conclusions: Herein we have describe five cases of HIT confirmed by the presence of a heparin-PF4 antibody and SRA testing. In all five cases the cause of thrombocytopenia was initially thought to be related to stem cell collection, which is known to cause a decline in platelets. It is notable that the platelet nadir in these patients, was frequently much lower than the nadir that is typically expected in HIT (50 to 80 x 109/L). Despite the development of thrombosis in two patients and the known increase in mortality in patients with HIT, the long term outcome in each of these patients was favorable. This is potentially attributable to rapid diagnosis, cessation of heparin, and initiation of alternative anticoagulation. In reaction to the initial cases, our institution has changed practices to eliminate heparin in the processing of stem cells so that all patients are able to receive their collected stem cells even in the setting of HIT. These cases highlight the existence of HIT during the process of HDM/SCT and the need for increased diligence in monitoring for unexpected thrombocytopenia or sluggish platelet recovery, in particular immediately after stem cell collection. Clinicians should have a low threshold to send diagnostic testing, begin alternative anticoagulation and postpone high dose chemotherapy in order to prevent life threatening complications. [Display omitted] DisclosuresSloan:Molecular Templates, Inc.: Consultancy; Stemline Pharmaceuticals: Consultancy.

Allogeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma Benefits Patients with Persistent Disease and Results in a High Rate of Residual Disease Clearance

Introduction: Residual disease (RD) after autologous transplantation as well as following induction therapy in multiple myeloma (MM) patients ineligible for transplant is associated with inferior survival. The significance of RD quantified by multiparameter flow cytometry (MFC) in the setting of allogeneic hematopoietic stem cell transplantation (HCT) for MM has not been reported. Using MFC we assessed the likelihood of RD clearance after HCT and assess whether RD status before HCT and at 1 and 3 months after HCT was associated with survival.Methods:We include 51 consecutive patients who underwent HCT for high-risk relapsed MM at our center between January 2014 and October 2016. All received CD34+ selected peripheral blood stem cell grafts. Donors included matched related (n=15), matched unrelated (n=20) and HLA 9/10 mismatched unrelated (n=16). The preparative regimen included busulfan (0.8mg/kg x 10 doses), melphalan (70mg/m2 x 2days), fludarabine (25mg/m2 x5days) and rabbit ATG (2.5mg/kg x 2 days).RD was assessed using MFC at 3 time points (TP) including TP0: median of 28 days (14-64) before transplantation (n=51), TP1: median of 28 days (range 26-55 days) after HSCT (n=48) and TP2: median 97 days (range 90-180days) after HSCT (n=43). MFC RD analysis was performed on marrow aspirate samples using 8-color flow analysis with sensitivity of 0.01% of white cells in 2013-till December 2015 and 10-color flow analysis with sensitivity of 0.0005% subsequently.Standard criteria were used to define categorical MM disease response. Overall survival (OS) was assessed using the Kaplan-Meier method and groups were compared using the log rank test. A landmark analysis was performed to assess the significance of MRD status at TP1 and TP2, with patients who relapsed or progressed within 30 days of the respective TP excluded from the landmark analysis.Results:Themedian age was 55 years (range 35-67). All patients had undergone prior autograft. Twelve experienced disease progression or relapse and 21 died, including 7 deaths due to relapsed MM and 14 due to transplant related mortality. The median follow-up amongst survivors (n=30) was 524 days (97-1089 days). Categorical disease status at HCT included: CR (n=9), VGPR (n=12), PR (n=21) and SD/PD (n=9) and this was associated with RD status. Detected RD was noted in 2/9 (22%), 8/12 (67%), 18/21 (86%) and 6/9 (67%) patients in CR, VGPR, PR and SD/PD, respectively (p=0.01).At TP0 34/51 had RD including all 13 with ≥5% marrow plasma cells. At TP1 31/48 were RD- (3 did not undergo RD assessment at TP1 due to TRM 49, 50 and 122 days after HCT). Of the 31 who were RD+ at TP0 and had assessment at TP1, 15 became RD- (48%). Sixteen of 17 who were RD- at TP0 remained RD- at TP1 and only 1 became RD+. Between TP1 and TP2 the concordance of MRD status among 43 patients who had assessment at both time points was 81% (RD+ at TP1 and TP2 n= 12, RD- at TP1 and TP2 n=23). Two became RD- at TP2 and 6 (14%) became MRD+, 4 of whom died due to MM.Categorical disease status before HCT was associated with RD status at TP1 and TP2. At TP1, 3/20 (15%) evaluable patients who were in CR or VGPR before HCT were RD+, compared to 14/28 (50%) who were in PR/SD or PD (p=0.016). At TP2, 3/19 (16%) evaluable patients who were in CR/VGPR prior to HCT were RD+ compared to 15/24 (63%) who were in PR/SD or PD (p=0.004). (Table 1)Conclusions: HCT resulted in the clearance of RD at TP1 in 48% of patients. Unlike autologous transplantation and pharmacologic therapy, HCT benefited MM patients irrespective of pre HCT RD status. Recurrence of RD by MFC was identified in 14% of patients between TP1 and TP2 suggesting this may be an optimal time to intervene with post transplant maintenance strategies. Improved RD sensitivity may be needed to better assess progression risk of MM post HCT. [Display omitted] DisclosuresKoehne:Atara: Consultancy, Patents & Royalties.

Update on a Phase II Study of Ixazomib with Lenalidomide As Maintenance Therapy Following Autologous Stem Cell Transplant in Patients with Multiple Myeloma

Update on a Phase II Study of Ixazomib with Lenalidomide As Maintenance Therapy Following Autologous Stem Cell Transplant in Patients with Multiple Myeloma

Clinical Outcomes of Catheter-Associated Venous Thrombosis in the Post-Hematopoietic Stem Cell Transplant Setting

Clinical Outcomes of Catheter-Associated Venous Thrombosis in the Post-Hematopoietic Stem Cell Transplant Setting

Posttransplantation Cyclophosphamide- and Sirolimus-Based Graft-Versus-Host-Disease Prophylaxis in Allogeneic Stem Cell Transplant

Post-transplantation cyclophosphamide (PTCy) has emerged as a promising graft-versus-host-disease (GVHD) prophylaxis in the setting of allogeneic hematopoietic stem cell transplantation (HSCT) from haploidentical donors and more recently in matched donor transplants. Herein, we describe our real-life experience on 249 adult patients undergoing allogeneic HSCT, from HLA-matched related (MRD), HLA-matched unrelated (MUD), or mismatched related donors (MMRD). Patients received unmanipulated peripheral blood stem cells (PBSCs), using a GVHD prophylaxis with PTCy and sirolimus. Mycophenolate mofetil was added in MUD or MMRD. In the HLA-matched donor group (MRD, n=48, MUD, n=50), the cumulative incidence of grades II-IV and III-IV acute GvHD was 23% and 9% at 100 days, respectively. The cumulative incidence of chronic GvHD was 25% at 2 years, severe only for 5% of the patients. The cumulative incidences of relapse and transplant-related mortality (TRM) were 31% and 9% at 2 years, respectively. The 2-year overall survival (OS) was 72% and progression-free survival (PFS) 60%; the composite endpoint of GvHD/relapse-free survival (GRFS) was 52% at 2 years. In the haploidentical donor group (n=151), we documented a cumulative incidence of grades II-IV and III-IV acute GVHD of 35% and 20% at 100 days, respectively, and a cumulative incidence of chronic GvHD of 39% at 2 years. We observed severe chronic GVHD in 15% of the patients. The cumulative incidence of relapse and TRM was 32% and 25% at 2 years, respectively. The 2-year OS was 48%, whereas PFS was 43%; GRFS was 28% at 2 years. However, more patients in the haploidentical group presented high/very high disease risk index (DRI) and higher HCT-comorbidity index. In patients classified in the low-intermediate DRI, 2-year GRFS was 53% in MRD, 65% in MUD, and 46% in haploidentical HSCT (P=.33). Sirolimus-PTCy platform deserves further investigation as an alternative to calcineurin-inhibitor-based GVHD prophylaxis for all donor sources. In patients presenting a low-intermediate DRI, this strategy translates in relevant survival independently from the transplant source.

Increased Mobility and Fall Reduction: An Interdisciplinary Approach on a Hematology-Oncology and Stem Cell Transplantation Unit.

Patients in the hematology-oncology and stem cell transplantation (SCT) setting are at high risk for functional decline and falls related to prolonged hospitalizations and inactivity during inpatient treatment. After underperforming on the Press Ganey National Database of Nursing Quality Indicators benchmark for falls in 2018, staff on a hematology-oncology and SCT unit implemented a practical and evidence-based fall prevention program. Fall rates from 2018 to 2019 ranged from 3.4 to 4.8 falls per 1,000 patient days. After the introduction of the unit-based gym program, early mobility increased and falls decreased to 2.57 per 1,000 patient days.

Proven and unproven cell therapies – what we have learned so far?

The exciting advancement in cell therapies in both cancer and regenerative medicine provides alternative therapeutic opportunities for patients with advanced diseases who have exhausted all treatment options. However, with the emergence of new technologies and innovations this also brings about “unproven” cell‐ and tissue‐based interventions that have not been fully evaluated in clinical trials. Such interventions have resulted in injuries and deaths in patients. Collectively, these practices increase the potential for patient exploitation and harm through the imposition of medical and financial risks. Recognizing this worrying situation, in April 2020, European Medicine Agency (EMA), committee for Advances Therapies advised patients and the general public to be cautious unproven cell‐based therapies. Likewise, the Food and Drug Administration (FDA) has posted information about products marketed as stem cells, mesenchymal stromal cells (MSCs) or other regenerative medicine products, including the conditions for which they are approved, and which products are not approved. Though both EMA and FDA recognize the promise of cell‐based therapies for treating patients with serious diseases, both concur that well‐designed clinical trials and regulatory oversight are necessary to ensure safety, efficacy and quality of the therapies. In this review, I will mention proven cell therapies in the haematopoietic stem cell transplant setting and in the form of chimeric antigen receptor (CAR) T‐cell therapies and briefly mention how these therapies have evolved over time, the learning curve and scientific progress in these therapies. I will then mention briefly about MSCs and focus on both the proven and unproven aspects of MSC.

DMSO (Me2SO) concentrations of 1-2% in combination with pentaisomaltose are effective for cryopreservation of T cells

T cell based treatments in the setting of allogenic haematopoietic stem cell transplantation (HSCT) have been used for decades. In addition, the use of chimeric antigen receptor (CAR) T cells has been introduced as a promising cancer immunotherapy. A prerequisite for many of these treatments is the ability to cryopreserve the cells safely and efficiently.In the present study, we compared freezing media combinations containing pentaisomaltose and 1–2 % DMSO (PIM1 and PIM2, respectively) to 10 % DMSO and commercially available cryosolutions (CS2 and CS10, Cryostor® containing 2 and 10 % DMSO, respectively) for cryopreservation of T cells.T cells isolated from buffy coats from healthy donors were cryopreserved with different freezing media and analysed for 1) viability immediately post-thaw and the following 24 h, 2) recovery, 3) proliferative potential and 4) migration towards a gradient of SDF-1α.The results showed that PIM2 was superior to 10 % DMSO and comparable to CS10 when assessing viability. Furthermore, the results indicated that the T cells cryopreserved with 10 % DMSO showed the lowest proliferative potential. The expression levels of CXCR3, CXCR4 and VLA-4 were similar in T cells independent of the freezing media used; however, T cells cryopreserved with PIM2 demonstrated the highest migratory potential.In summary, the combination of pentaisomaltose and 1–2 % DMSO improves the cryoprotective properties compared to 10 % DMSO while achieving comparable results with CS10 and even showing improved migration towards SDF-1α. Thus, our results show promising potential for pentaisomaltose in combination with low amounts of DMSO for the cryopreservation of T cells.

Does Mesenchymal Stromal Cell Count in Pre-autologous Hematopoietic Stem Cell Transplant Peripheral Blood and Apheresis Product Predict for Infectious Complications in the Post-transplant Period?

Mesenchymal stromal cells (MSC) have gained attention in the recent past considering their multipotentiality and organ-healing properties. Exogenous administration of MSC in the pre-hematopoietic stem cell transplant (HSCT) setting has been reported to enhance engraftment, heal graft-vs-host disease and increase infections in the post-HSCT period. In this study, we aimed to determine the effect of endogenous pre-HSCT MSC on the post-HSCT infectious complications in patients undergoing autologous-HSCT. The study included patients undergoing autologous-HSCT (n = 25; multiple myeloma-20, lymphoma-5). MSC were analyzed and quantified by flow cytometry in the peripheral blood (PB) at baseline, and in both PB and apheresis product (AP) following mobilization with growth factors. Pre-HSCT MSC (PB/AP) were correlated with the post-HSCT duration of febrile neutropenia and duration of antimicrobial drugs using Pearson's correlation co-efficient, and with the mucositis grade using Spearman's rank correlation. Pre-HSCT MSC (baseline and post-mobilization) correlated positively with the longer duration of febrile neutropenia and duration of antimicrobials used in the post-HSCT period (p < 0.05). Pre-HSCT MSC failed to correlate with post-HSCT engraftment and onset/severity/duration of oral and gastrointestinal mucositis. Endogenous pre-HSCT MSC counts might predict for increased infectious complications in the post autologous-HSCT setting.

Antimicrobial therapy during cancer treatment: Beyond antibacterial effects.

Cancer treatment options have evolved to include immunotherapy and targeted therapy, in addition to traditional chemoradiation. Chemoradiation places the patient at a higher risk of infection through a myelosuppressive effect. High clinical suspicion and early use of antimicrobials play a major role in decreasing any associated morbidity and mortality. This has led to a widespread use of antimicrobials in cancer patients. Antimicrobial use, however, does not come without its perils. Dysbiosis caused by antimicrobial use affects responses to chemotherapeutic agents and is prognostic in the development and severity of certain cancer treatment-related complications such as graft-versus-host disease and Clostridioides difficile infections. Studies have also demonstrated that an intact gut microbiota is essential in the anticancer immune response. Antimicrobial use can therefore modulate responses and outcomes with immunotherapy targeting immune checkpoints. In this review, we highlight the perils associated with antimicrobial use during cancer therapy and the importance of a more judicious approach. We discuss the nature of the pathologic changes in the gut microbiota resulting from antimicrobial use. We explore the effect these changes have on responses and outcomes to different cancer treatment modalities including chemotherapy and immunotherapy, as well as potential adverse clinical consequences in the setting of stem cell transplant.

Allogeneic haematopoietic stem cell transplantation from SARS-CoV-2 positive donors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19, but up to half of people infected with the virus are asymptomatic.1 Moreover, SARS-CoV-2 RNAemia might occur in about 15% of symptomatic patients but also in a minority of those who are asymptomatic,2 making possible—yet unconfirmed to date—the possibility of viral transmission through blood products,3,4 in particular in the setting of allogeneic haematopoietic stem cell transplantation (HSCT).

Prognostic Impacts of D816V KIT Mutation and Peri-Transplant RUNX1-RUNX1T1 MRD Monitoring on Acute Myeloid Leukemia with RUNX1-RUNX1T1.

Simple SummaryAcute myeloid leukemia (AML) with RUNX1-RUNX1T1 is a heterogeneous disease entailing different prognoses. Patients with high-risk features can benefit from allogeneic hematopoietic stem cell transplantation (HSCT) or autologous HSCT. However, insufficient data about major risk factors, such as KIT mutations and measurable residual disease (MRD) status for relapse, make it difficult to clarify the benefit of each transplant strategy. Moreover, limited data are available to elucidate the exact prognostic impacts of different types of KIT mutations and optimal thresholds or time points for RUNX1–RUNX1T1 MRD assessment, particularly in the setting of HSCT. Given the lack of prospective study, the current retrospective study, including a large cohort of high-risk AML patients with RUNX1–RUNX1T1, firstly demonstrated the differentiated prognostic impact of D816V KIT mutation among various KIT mutations and clarified optimal time points and thresholds for RUNX1–RUNX1T1 MRD monitoring in the setting of HSCT.The prognostic significance of KIT mutations and optimal thresholds and time points of measurable residual disease (MRD) monitoring for acute myeloid leukemia (AML) with RUNX1-RUNX1T1 remain controversial in the setting of hematopoietic stem cell transplantation (HSCT). We retrospectively evaluated 166 high-risk patients who underwent allogeneic (Allo-HSCT, n = 112) or autologous HSCT (Auto-HSCT, n = 54). D816V KIT mutation, a subtype of exon 17 mutations, was significantly associated with post-transplant relapse and poor survival, while other types of mutations in exons 17 and 8 were not associated with post-transplant relapse. Pre- and post-transplant RUNX1–RUNX1T1 MRD assessments were useful for predicting post-transplant relapse and poor survival with a higher sensitivity at later time points. Survival analysis for each stratified group by D816V KIT mutation and pre-transplant RUNX1–RUNX1T1 MRD status demonstrated that Auto-HSCT was superior to Allo-HSCT in MRD-negative patients without D816V KIT mutation, while Allo-HSCT was superior to Auto-HSCT in MRD-negative patients with D816V KIT mutation. Very poor outcomes of pre-transplant MRD-positive patients with D816V KIT mutation suggested that this group should be treated in clinical trials. Risk stratification by both D816V KIT mutation and RUNX1–RUNX1T1 MRD status will provide a platform for decision-making or risk-adapted therapeutic approaches.

A qualitative study of pediatric nurses' perception of factors affecting negotiation of care in a pediatric stem cell transplant unit.

The adoption of a 'family-centered-care' philosophy is essential for the care process and its negotiation. A better understanding of nurses' perception of factors that affect the process of negotiation could allow us to better address future interventions and to improve FCC. The purpose of our study was to investigate pediatric nurses' perception of factors that affect the process of negotiation of care with Stem Cell Transplantation pediatric patients and their parents. A qualitative research design with in-depth interviews was chosen. Sixteen interviews (16 nurses) were audio recorded and transcribed verbatim. Two researchers conducted independently a thematic analysis of the verbatim transcripts of the interviews. Four themes emerged from the data as factors that affect the process of negotiation: (a) communication, (b) personal factors (c) specificity, and (d) organization. These themes represent interesting points for future improvement interventions. Negotiation in the Stem Cell Transplant setting would deserve further research, with special focus on children' and parents' perception of factors affecting this important aspect. Furthermore, in the future, negotiation guidelines could be validated and implemented effectively and an already validated tool could be used to document the negotiation process in the Stem Cell Transplant setting.

Mitigation of in-hospital risk of coronavirus disease 2019: Experience from a haematology-oncology and stem cell transplant setting.

. Coronavirus disease 2019 (Covid-19) was first described in December 2019 and has evolved into an ongoing global pandemic. Cancer patients on chemotherapy are immunocompromised and are at the highest risk of Covid-19-related complications. We describe our experience with the management of haematology-oncology and stem cell transplant (SCT) patients receiving curative chemotherapy in a hospital with a high influx of Covid-19 patients. . We did a prospective observational study at a 99-bedded cancer centre of a tertiary care teaching hospital from April 2020 to September 2020. Preventive measures taken were categorized as follows: (i) staff: screening, mandatory use of personal protective equipment (PPE), risk stratification of potential exposure and testing and isolation as needed; (ii) patients: mandatory viral polymerase chain reaction testing, segregation of positive and untested patients and testing of family members; and (iii) environment: mandatory regular cleaning, visitor restriction, telemedicine services and reassignment of priority to clinic visits. Treatment of the underlying conditions was continued with added precautions. . A total of 54 patients were included in the analysis, including 48 with haematological malignancies and 6 for stem cell therapy. Preventive measures were universally applied, and chemotherapy with a curative intent was initiated as per protocol. Three patients were detected to have Covid-19 infection before admission and one after the institution of chemotherapy. Nine patients died after the first cycle of chemotherapy, 2 due to severe Covid-19-related illness and 7 due to complications of chemotherapy or disease progression. . In the wake of the Covid-19 pandemic, treatment for haematological malignancies must continue while balancing the risk of Covid-19 infections. Our report emphasizes the effectiveness of measures such as hand hygiene, social isolation, patient segregation, use of masks and PPE and universal pre-treatment testing for Covid-19 in reducing the risk of infection in a high-risk clinical setting.

Use of Sysmex Hematology Analyzer based Hematopoietic Progenitor Cell (XN-HPC) Count in Allogeneic Peripheral Blood Stem Cell Transplant Setting; Is It Substantially Reliable?

Allogeneic stem cell transplantation remains the only curative option for various benign and malignant hematological disorders. The procedure of allogeneic stem cell transplantation entails the administration of adequate doses of hematopoietic progenitor cells, aiming for complete and sustained hematopoietic reconstitution. Hematopoietic progenitors are obtained either through a bone marrow harvest or from GCSF-mobilized peripheral blood of the identified donor. Over the years various modalities have been utilized to establish the adequacy of harvested stem cell product e.g. Colony-forming unit– granulocyte monocyte (CFU-GM) assay, total mononuclear cell count (MNC), and CD34+ cell count

The Pattern of Cyclosporine Nephrotoxicity and Urinary Kidney Injury Molecule 1 in Allogenic Hematopoietic Stem Cell Transplant Patients

The typical immunosuppressive regimen of hematopoietic stem cell transplant includes cyclosporine. However, cyclosporine nephrotoxicity is a concern. We studied cyclosporine nephrotoxicity epidemiology in hematopoietic stem cell transplant patients and compared the pattern and urinary levels of the KIM-1 kidney injury molecule versus serum and urine creatinine levels. The study covered 10 months at Namazi Hospital, Shiraz, Iran. All patients met the following criteria: > 15 years old, received allogenic hematopoietic stem cell transplant without history of acute or chronic kidney disease, and scheduled for at least 1 week of cyclosporine treatment. Urinary and serum levels of creatinine, urea, sodium, potassium, magnesium, and the KIM-1 kidney injury molecule were measured on days 0, 3, 5, 7, 10, and 14 of cyclosporine treatment. Of 42 patients, one-third developed cyclosporine nephrotoxicity (30.95%), and median onset time was 15 days. Hypokalemia and hypomagnesemia were reported in 76.2% and 53.4% of the cohort, respectively. None of the demographic, clinical, and paraclinical parameters was significantly associated with cyclosporine nephrotoxicity. Median duration of hospital stay for patients with cyclosporine nephrotoxicity (41 days) was significantly higher (P < .001) than those without nephrotoxicity (29 days). Area under the curve for receiver operating characteristic showed that accuracy of serum creatinine (0.267; 95% CI, 0.11-0.43) at day 0 of cyclosporine treatment was significantly lower (P = .017) than the accuracy of urine creatinine (0.477; 95% CI, 0.28-0.67) and urine levels of the KIM-1 kidney injury molecule (0.594; 95% CI, 0.41-0.78). Cyclosporine nephrotoxicity is a common adverse effect in the setting of hematopoietic stem cell transplant and occurs mostly within the first 2 weeks of cyclosporine treatment. Urine KIM-1 kidney injury molecule measurement had no overall superiority and no improved accuracy over serum or urine creatinine measurements for prediction or detection of cyclosporine nephrotoxicity.

Alemtuzumab Versus Anti-Thymocyte Globulin As Conditioning Method for Allogenic Hematopoietic Stem Cell Transplant; A Meta-Analysis

Objective: Anti-thymocyte Globulin (ATG) and Alemtuzumab (Ale) are common methods for T cell depletion in the setting of allogenic hematopoietic stem cell transplant. They are both used to promote engraftment and prevent graft-versus-host disease (GVHD). Currently, there's no comparative meta-analysis for safety and efficacy of Ale versus ATG. Therefore, we conducted a meta-analysis to compare the risk of acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), odd of relapse and overall survival (OS) between Ale and ATG. Method: We performed a comprehensive literature search in MEDLINE (Pubmed), Cochrane library and EMBASE database from inception to April 2020 for studies that compared the use of Ale and ATG. We conducted a random effect meta-analysis of 11 studies involving a total of 4,239 participants (Ale=1,293, ATG=2,946) and reported the pooled odd ratio (OR) for development of aGVHD, cGVHD, relapse and OS. Result: We found a significant decreased in odd of aGVHD and cGVHD in the Ale group compared to the ATG group (pooled OR 0.44, 95% CI 0.32-0.61, I2=56.1% and 0.58, 95% CI 0.44-0.77, I2=47.5% respectively) but there were no statistically significant increase in the odd of relapse and OS (pooled OR 1.14, 95% CI 0.81-1.59, I2=64.5% and 1.20, 95% CI 0.83-1.72, I2=76.3% respectively). Conclusion: There is significantly decreased odd of aGVHD and cGVHD with use of Ale compared to ATG, but there is no statistically significant increased odd of relapse or OS. We concluded that Ale could be the superior method of T cell depletion in terms of decreased aGVHD and cGVHD but there's no significant difference in odd of relapse and OS. Disclosures No relevant conflicts of interest to declare.

Evaluating the PET Parameters SUVmax and TMTV in the Setting of Autologous Stem Cell Transplantation for DLBCL

Introduction Where tolerated,high dose chemotherapy supported by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). Disease recurrence post-ASCT however is common and carries an extremely poor prognosis, highlighting the need for improved pre-transplant prognostic stratification. This study investigates the prognostic utility of the PET parameters total metabolic tumour volume (TMTV) and standardised uptake value (SUV)max in the peri-transplant setting. Methods 125 patients underwent ASCT for relapsed or refractory DLBCL between 1/1/2002 and 31/1/2017 at the Peter MacCallum Cancer Centre. All patients received multi-agent salvage immuno-chemotherapy before proceeding to ASCT. 58 patients were treated with peri-transplant radiotherapy, with indications including incomplete response post-salvage therapy, and bulky and/or localised disease. 122 patients had their treatment response assessed with PET. TMTV and SUVmax were measured at time of primary disease relapse/progression prior to salvage immuno-chemotherapy (pre-salvage PET) and post-salvage immuno-chemotherapy prior to ASCT (pre-ASCT PET). 93 patients had pre-salvage and pre-ASCT PETs available for TMTV and SUVmax measurement. Results Median follow up was 5.6 years. The 5-year progression free survival (PFS) and overall survival (OS) were 52% (95% CI: 42-60) and 65% (95% CI: 56-73). In patients demonstrating complete metabolic response (CMR) and non-CMR on pre-ASCT PET the 5-year PFS was 58% (95% CI: 44-70) and 44% (95% CI: 29-57) respectively. The 5-year OS with CMR and non-CMR on pre-ASCT PET was 73% (95% CI: 59-83) and 54% (95% CI: 39-67). TMTV and SUVmax were investigated as potential prognostic factors in the peri-transplant setting. In this patient group, pre-salvage TMTV and SUVmax were not found to be of prognostic significance. Pre-salvage TMTV and SUVmax PFS hazard ratios (HR)s were 1.06 per 100ml (95% CI:0.96-1.17; p = 0.27) and 1.00 (95% CI: 0.98-1.03; p = 0.78) respectively, and OS HRs were 1.10 per 100ml (95% CI: 0.86-1.18; p = 0.07) and 1.02 (95% CI: 0.96-1.04 p = 0.24). In contrast, pre-ASCT TMTV was a significant negative prognostic factor for both PFS (HR = 1.22 per 100ml; 95%CI: 1.10-1.37; p &amp;lt; 0.001) and OS (HR = 1.96 per 100ml; 95% CI: 1.38-2.79; p &amp;lt; 0.001). Pre-ASCT SUVmax similarly demonstrated a negative association with PFS (HR = 1.07; 95% CI: 1.04-1.10; p &amp;lt; 0.001) and OS (HR of 1.08 ; 95% CI: 1.04-1.11; p &amp;lt; 0.001). In addition to the TMTV and SUVmax absolute values, the relative change from pre-salvage to pre-ASCT PET was investigated for prognostic value. No significant association with PFS or OS was demonstrated for the relative change of either parameter. The relative change in TMTV had a HRs of 1.21 (95% CI: 0.54- 2.72; p = 0.65) and 1.15 (95% CI: 0.45-2.93; p = 0.77) for PFS and OS respectively, and relative change in SUVmax had a HRs of 1.30 (95% CI: 0.68- 2.50; p = 0.43) and 1.20 (CI 95% 0.57-2.54; p = 0.64) for PFS and OS. Conclusion As prognostic tools, pre-ASCT TMTV and SUVmax were both predictors for PFS and OS. In contrast, pre-salvage TMTV and SUVmax did not demonstrate an association with PFS or OS, reinforcing the prognostic significance of the pre-ASCT PET scan. The relative change in SUVmax and TMTV were similarly not associated with PFS and OS. These findings indicate that in the context of TMTV and SUVmax measurement, residual disease on pre-ASCT PET may be of greater predictive value than degree of response to salvage immuno-chemotherapy. While TMTV and SUVmax have primarily been studied in the context of first-line therapy for DLBCL, these results suggest a promising prognostic role for these PET parameters in the peri-transplant setting. Disclosures Seymour: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Consultancy; Nurix: Honoraria; Mei Pharma: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria. Dickinson:Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck Sharp &amp; Dohme: Consultancy; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.