Allogeneic Transplant Patients Research Articles

USING 6-MINUTE WALKING DISTANCE AND FRAILTY MEASURES TO PREDICT RISK OF POSTSTEM CELL TRANSPLANT PULMONARY COMPLICATIONS AND MORTALITY

USING 6-MINUTE WALKING DISTANCE AND FRAILTY MEASURES TO PREDICT RISK OF POSTSTEM CELL TRANSPLANT PULMONARY COMPLICATIONS AND MORTALITY

Patient age and donor HLA matching can stratify allogeneic hematopoietic cell transplantation patients into prognostic groups.

Mixed results surround the accuracy of commonly used prognostic risk scores to predict overall survival (OS) and non-relapse mortality (NRM) in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. We hypothesize that a simple prognostic score performs better than conventional scoring systems. OS risk factors, HCT-CI, age-HCT-CI, and augmented-HCT-CI were studied in 299 patients who underwent allo-HCT for myeloid and lymphoid malignancies. A scoring system was developed based on results and validated in a different cohort of 455 patients. Two-year OS was 51% (95% confidence interval (CI) 0.45-0.56); 2-year NRM was 34% (95% CI 0.29-0.39). HCT-CI and associated scores were grouped into 0-2 and ≥3. Age and HLA mismatch status were the only risk factors to affect OS in multivariate analysis (p= 0.02 and 0.05, respectively). HCT-CI and associated scores were not informative for OS prediction. The weighted scoring system assigned 0 to 2 points for age < 50, 50-64, or ≥65, respectively, and 0-1 points for no HLA mismatch versus any mismatch (except HLA-DQ). Distinct 2-year OS (62%, 53%, and 38% [p= <0.001]) and NRM (24%, 34%, and 43% [p= 0.02]) groups were characterized. The scoring system was validated in a second independent cohort with similar results on OS and NRM (p< 0.001). A simple scoring system based on recipient's age and mismatch status accurately predict OS and NRM in two distinct cohorts of allo-HCT patients. Its simplicity makes it a helpful tool to aid clinicians and patients in clinical decision-making.

Overall Survival Rate in Allogeneic Stem Cell Transplanted Patients Requiring Intensive Care Can Be Predicted by the Prognostic Index for Critically Ill Allogeneic Transplantation Patients (PICAT) and the Sequential Organ Failure Assessment (SOFA) Scores.

Simple SummaryIntensive care admission is a common complication of allogeneic hematopoietic stem cell transplantation. Mortality remains very high, and among several prognosis tools, data about power of discrimination showed contradictory results. The aim of our retrospective study was to evaluate the efficacy of a new score, the Prognostic Index for Critically Ill Allogeneic Transplantation (PICAT) Patients, for this specific setting in a cohort of 111 patients. We confirmed the ability of this score to discriminate three groups of patients with different outcomes. Moreover, we evaluated a classic intensive score, the Sequential Organ Failure Assessment (SOFA), and we showed that the SOFA outperformed the PICAT to predict outcomes in our cohort.Background. Allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients requiring intensive care unit (ICU) have high mortality rates. Methods. In the current study, we retrospectively assessed whether the Prognostic Index for Critically Ill Allogeneic Transplantation patients (PICAT) score predicted overall survival in a cohort of 111 consecutive allo-HCT recipients requiring ICU. Results. Survival rates at 30 days and 1 year after ICU admission were 57.7% and 31.5%, respectively, and were significantly associated with PICAT scores (p = 0.036). Specifically, survival at 30-day for low, intermediate, and high PICAT scores was 64.1%, 58.1%, and 31.3%, respectively. At one-year, the figures were 37.5%, 29%, and 12.5%, respectively. In multivariate analyses, high PICAT score (HR = 2.23, p = 0.008) and relapse prior to ICU admission (HR = 2.98, p = 0.0001) predicted higher mortality. We next compared the ability of the PICAT and the Sequential Organ Failure Assessment (SOFA) scores to predict mortality in our patients using c-statistics. C statistics for the PICAT and the SOFA scores were 0.5687 and 0.6777, respectively. Conclusions. This study shows that while the PICAT score is associated with early and late mortality in allo-HCT recipients requiring ICU, it is outperformed by the SOFA score to predict their risk of mortality.

Drug-induced Fanconi syndrome in patients with kidney allograft transplantation

BackgroundPatients after kidney transplantation need to take long-term immunosuppressive and other drugs. Some of these drug side effects are easily confused with the symptoms of Fanconi syndrome, resulting in misdiagnosis and missed diagnosis, and causing serious consequences to patients. Therefore, improving awareness, early diagnosis and treatment of Fanconi syndrome after kidney transplantation is critical.MethodsThis retrospective study analyzed 1728 cases of allogeneic kidney transplant patients admitted to the Second Xiangya Hospital of Central South University from July 2016 to January 2021. Two patients with Fanconi syndrome secondary to drugs, adefovir dipivoxil (ADV) and tacrolimus, were screened. We summarized the diagnostic process, clinical data, and prognosis.ResultsThe onset of Fanconi syndrome secondary to ADV after renal transplantation was insidious, and the condition developed after long-term medication (>10 years). It mainly manifested as bone pain, osteomalacia, and scoliosis in the late stage and was accompanied by obvious proximal renal tubular damage (severe hypophosphatemia, hypokalemia, hypocalcemia, hypouricemia, glycosuria, protein urine, acidosis, etc.) and renal function damage (increased creatinine and azotemia). The pathological findings included mitochondrial swelling and deformity in renal tubular epithelial cells. The above symptoms and signs were relieved after drug withdrawal, but the scoliosis was difficult to rectify. Fanconi syndrome secondary to tacrolimus has a single manifestation, increased creatinine, which can be easily confused with tacrolimus nephrotoxicity. However, it is often ineffective to reduce the dose of tacrolomus, and proximal renal failure can be found in the later stage of disease development. There was no abnormality in the bone metabolism index and imageological examination findings. The creatinine level decreased rapidly, the proximal renal tubule function returned to normal, and no severe electrolyte imbalance or urinary component loss occurred when the immunosuppression was changed from tacrolimus to cyclosporine A.ConclusionsFor the first time, drug-induced Fanconi syndrome after kidney transplantation was reported. These results confirmed that the long-term use of ADV or tacrolimus after kidney transplantation may have serious consequences, some of which are irreversible. Greater understanding of Fanconi syndrome after kidney transplantation is necessary in order to avoid incorrect and missed diagnosis.

Busulfan and cyclophosphamide‐based conditioning regimen still holds the promise of being a safe and efficacious regimen for allogeneic transplantation in patients with transfusion‐dependent thalassemia, even in high risk

Busulfan and cyclophosphamide (BuCy)-based regimen has been used as a standard myeloablative chemotherapy for haematopoietic stem cell transplantation in thalassemia. However, treosulfan-based conditioning regimen has emerged due to concerns of toxicities. We retrospectively analysed the safety and efficacy of fludrabine/Bu/Cy/antithymocyte globulin (ATG) versus treosulfan/thiotepa/fludrabine regimens for Hematopoietic Stem Cell Transplant (HSCT) in transfusion-dependent thalassemia (TDT) conducted at our institute (2013-2021). In 75 patients, 36 (48%) received Flu/Bu/Cy/ATG whereas 39 (52%) received Treo/Thio/Flu. Median age was 6 (1-12) and 9 (1-15) years, respectively. Number of patients with Classes I, II, and III were 14, 10, and 12 in Flu/Bu/Cy/ATG versus 2, 19, and 18 in Treo/Thio/Flu group, respectively. Graft was growth factor mobilized bone marrow in Flu/Bu/Cy/ATG versus peripheral blood stem cell in Treo/Thio/Flu group. Mean stem cell dose was 3.82 (2.2-9.1) versus 5 (1.65-8.01)106 /kg in Flu/Bu/Cy/ATG versus Treo/Thio/Flu group, respectively. Neutrophils and platelets engrafted at a median of 16 (14-21) and 16 (9-47) days in Flu/Bu/Cy/ATG and 15 (10-20) and 13 (9-41) days in Treo/Thio/Flu group. Median duration of follow-up was 28 (23-32.9) months. Five (6.6%) patients had rejection (all secondary). Venoocclusive disease was observed in 2 (5.7%) versus 4 (10.3%) patients (p=.047), respectively. Flu/Bu/Cy/ATG had 4 (11.4%) patients with acute GVHD versus 15 (38.5%) patients which had significant impact on survival (p=.038). We observed chronic GVHD in 4 (11.4%) and 11 (28.2%) patients, respectively, with significant impact on survival (p=.031). Four (5.1%) patients had TRM in Treo/Thio/Flu group, in contrast to none in Flu/Bu/Cy/ATG group. Mixed chimerism was common in Flu/Bu/Cy/ATG {20 (57.1%)} versus Treo/Thio/Flu group {12 (30.1%)}. Five-year Event Free Survival (EFS) and OS of entire cohort were 87% + 4% and 94% + 3%, respectively. Estimated TFS, EFS, OS of Flu/Bu/Cy/ATG versus Treo/Thio/Flu was 97.1% + 2.9% versus 89.2% + 5.1% (p=.251), 97 + 3% versus 80.7 + 6% (p=.041) and 100% versus 90.4 + 5% (p=.067), respectively. In our experience, Flu/Bu/Cy/ATG regimen is safe and effective even in high-risk TDT. However, one needs to be vigilant for mixed chimerism.

Kinetics of disappearance and appearance of isoagglutinins A and B after ABO-incompatible hematopoietic stem cell transplantation

ABO-incompatible allogeneic hematopoietic stem cell transplantation (HSCT) can be complicated by poor red cell engraftment and hemolysis, both mediated by isoagglutinins. Anecdotally, isoagglutinins indicates an activation of donor’s immunity or even relapse. Consequently, the routine monitoring of isoagglutinins could help physicians to predict the risk of complications. The purpose of this study is to investigate the time to disappearance and appearance of isoagglutinins after ABO-incompatible allogeneic HSCT. In a one-year follow-up, data of 136 ABO-incompatible hematopoietic stem cell (HSC) allogeneic transplanted patients were studied, of which 60 had major, 61 minor and 15 bidirectional incompatibility. Survival analyses were conducted and association with hematological diseases, HLA-compatibility and transplantation strategy was investigated. We observed a disappearance of isoagglutinin A in 82.0% of cases at one year with a median and 75th percentile of 38.4 and 138.6 days, respectively. For isoagglutinin B, these same values were 96.4%, 15.9 and 29.1 days, respectively. The appearance of isoagglutinin A occurred in 10.7% of cases. Disappearance of isoagglutinin A was significantly slower in patients with myeloid diseases compared to other diseases. The results of this study provide useful values to detect early risks of preventable immunohematological complications and possibly, in exceptional cases, relapse.

P1572: IMPACT OF GUT COLONIZATION BY GRAM NEGATIVE MULTIRESISTANT BACTERIA IN PATIENTS WITH ACUTE LEUKEMIA UNDERGOING INTENSIVE ANTINEOPLASTIC TREATMENT

Background: Gut colonization by Gram negative multiresistant bacteria (GNMRB) occurring during chemotherapy treatment for acute leukemia (AL) reduces overall survival (OS) by increasing early non-relapse mortality (NRM). The impact of colonization once patients have finished antineoplastic treatment is unknown. Aims: To evaluate long-term consequences of GNMRB colonization on AL surviving patients. Methods: Retrospective study including all consecutive AL patients treated with standard intensive chemotherapy with or without Hematopoietic Stem Cell Transplant (HSCT) who completed first line antineoplastic treatment. A landmark analysis was performed including all patients alive 60 days after last chemotherapy cycle of HSCT. Primary end point was OS. Secondary end points were non-relapse mortality (NRM) and acute (a) and chronic (c) Graft Versus Host Disease (GVHD) in allogeneic transplanted patients. Data are presented as median (interquartile range) or proportion. Cumulative incidence of NRM was calculated accounting for the competing risk of leukemic-death. Survival curves were built using the Kaplan-Meir method and univariate analysis was performed using the Log-Rank test. Statistical analysis was performed using the R 4.1.1 software package. Results: From April 2016 to March 2021, 142 patients from a single center were treated with intensive chemotherapy, of whom 96 were alive 60 days after chemotherapy or HSCT. Median age was 55 (42-52) years with 50% (48/96) of female patients. ECOG performance status at diagnosis of the disease was 0-1 in 98% (94/96) patients. A diagnosis of Acute Myeloid Leukemia (AML), high-risk Myelodysplastic Syndrome and Acute Lymphoblastic Leukemia (ALL) was present in 85% (82/96), 1% (1/96) and 14 (14/96) patients, respectively. Hematopoietic Transplant Comorbidity Index (HCTCI) was low, intermediate and high in 68% (66/96), 16% (16/96) and 16% (16/96) patients, respectively. Within AML patients, ELN17 genetic risk was favourable, intermediate and adverse in 48% (38/79), 18% (14/79) and 34% (27/79) patients. Prophylactic fluoroquinolones were used in 65% (62/96) patients, significantly more used in AML/MDS than in ALL patients: 69% (57/83) vs 38% (5/13), respectively, P=0.03. Throughout the first line treatment, 48% (46/96) patients were colonized by GNMRB, being the recovered microorganisms: Klebisella sp. 61% (28/46), Enterobacter sp: 17%, (8/46), Citrobacter sp: 11% (5/46), E. Coli: 9% (4/46), and Pseudomonas aeruginosa 2% (1/46). With a median follow up of 17 (7-34) months, there were no differences in univariate analysis of OS between colonized compared to non-colonized patients: [53 months (95% CI: 26-NR) vs NR (95% CI: 26-NR), P= 0.9], (Figure). On the contrary, age and ELN17 genetic risk were significantly associated with OS (Table). Additionally, no differences in aGVHD [34% (10/29) vs 45% (10/22)], P=0.4, or cGVHD [18% (4/22) vs 14% (4/29), P=0.9] were observed between colonized and non-colonized patients. Regarding NRM, a non-significant increase in non-leukemic deaths were observed in colonized patients compared to non-colonized patients: 15% (7/46) vs 8% (4/46) P= 0.6. - Overall Survival Yes No P Age>65 yo 24.6 (12-NR) NR (53-NR) 0.01 ELN genetic risk 0.001 - Favorable NR (NR-NR) - - Intermediate 20.6 (6.8-NR) - - Adverse 26.6 (17.7-NR) Colonization 53.2 (26-NR) NR (26-NR) 0.9 Image:Summary/Conclusion: Gram negative multiresistant bacteria gut colonization is not associated with worse long-term outcomes in acute leukemia patients compared to non-colonized patients.

Lower expression of NOTCH components in peripheral blood mononuclear cells of allogeneic hematopoietic cell transplant patients

IntroductionChronic graft-versus-host disease (cGvHD) not only remains the main cause of late mortality after allogeneic hematopoietic cell transplant, but also has the capacity of causing severe organ impairment in those who survive. The Notch, a highly conserved ligand-receptor pathway, is involved in many immunological processes, including inflammatory and regulatory responses. Recently, mouse models have shown that the blockage of canonical Notch signaling prevents GvHD. Objective and MethodDue to the lack of data on the Notch pathway in human chronic GvHD, we sought to study the expression of NOTCH components in primary samples of patients who received allo-HCT and presented active cGvHD or a long-term clinical tolerance to cGvHD. ResultsOur results showed a significantly lower expression of NOTCH components in both groups that received allo-HCT, independently of their cGvHD status, when compared to healthy controls. ConclusionMoreover, there were no differences in gene expression levels between the active cGvHD and clinically tolerant groups. To our knowledge, this is one of the first studies performed in human primary samples and our data indicate that much remains to be learned regarding NOTCH signaling as a new regulator of GvHD.

Palliative care pilot initiative for transplant patients: The Westchester Medical Center experience.

e19050 Background: It is well known HCT recipients experience multiple symptoms affecting quality of life. Emerging data supports the role palliative care can play in mitigating these issues. Our cellular therapy team collaborated with the Palliative Care team on a pilot project incorporating their expertise into the management of our new allogeneic transplant patients. We chose this group of patients given their increased needs relative to other cellular therapy recipients (i.e. autologous, CTL) and our institution’s available resources. Methods: Patients admitted to the HCT unit for allogenic stem cell transplant underwent palliative care consult during their conditioning regimen. During the initial palliative care visit, performed by a specialist palliative care nurse practitioner, patients underwent comprehensive assessment of physical symptoms, psychosocial distress, and overall quality of life. Patients were then followed during hospitalization by members of the palliative care team including Nurse Practitioner, Social Worker and Chaplain, to address identified needs and support both the patient and their family. The palliative care team provided daily communication and recommendations to our inpatient HCT team. Results: Patient one was a 61-year-old man with intermediate risk MDS who underwent a reduced intensity conditioning regimen of busulfan, fludarabine, and alemtuzumab. His transplant was complicated by delirium and anorexia. Patient two was a 63-year-old man with AML who underwent a reduced conditioning regimen of the same combination. His transplant was complicated by bone pain and insomnia. Patient three was a 70-year-old woman with AML who also underwent a reduced conditioning regimen. Her transplant was complicated by severe mucositis and gastric reflux. Conclusions: Allogeneic stem cell transplant patients experience a multitude of symptoms and psychosocial distress. With the help of a dedicated palliative care assessment, we can improve patients’ quality of life during their admission for the transplant. Considering the positive feedback from patients, we plan to conduct a formal prospective study evaluating the impact of palliative care on adult stem cell transplant patients at our institution. By addressing the patient’s whole person rather than just their disease, we also hope to decrease number of admissions as well as length of stay. Ultimately, we look forward to expanding this to other malignancies as well.

Successful neutrophil engraftment supported by granulocyte transfusion in adult allogeneic transplant patients with peri-transplant active infection

Active infection at the time of allogeneic hematopoietic stem cell transplantation (HSCT) is a risk for non-relapse mortality (NRM) after HSCT. Granulocyte transfusion (GTX) has been used to prevent or treat life-threatening infections in patients with severe neutropenia. However, data are limited on the clinical benefits of GTX during HSCT. We retrospectively analyzed the transplant outcomes of HSCT patients who had undergone GTX between 2012 and 2020. Altogether, 20 patients with documented infection had received 55 GTXs during HSCT. No adverse events were observed during the GTX infusion. The average number of granulocytes was 0.40 (range, 0.10–1.59) × 109/kg. The median neutrophil increment one day after GTX was 515 (range, −6 to 6630)/μl, which was significantly correlated with the infused granulocyte dose (p = 0.0007). A total of 17 of 20 patients achieved neutrophil engraftment. The number of infused granulocytes tended to higher in clinical responders (p = 0.12), and patients receiving ≥ 0.5 × 109/kg showed trend toward to better transplant outcomes (GTX-high vs. GTX-low, 1-year OS; 33% vs. 11%, p = 0.19. 1-year NRM; 44% vs.77%, p = 0.11). The type of red blood sedimenting agents was significantly correlated with the amounts of granulocyte collection. In conclusion, GTX, especially with a high amount of containing granulocytes, could be a safe bridging therapy for neutrophil engraftment after HSCT in patients with active infection.

Prevalence of Clostridium difficile Infection in the Hematopoietic Transplantation Setting: Update of Systematic Review and Meta-Analysis.

Hematopoietic stem cell transplant (HSCT) recipients are vulnerable to Clostridium difficile infection (CDI) due to risk factors such as immunosuppression, antimicrobial use, and frequent hospitalization. We systematically searched PubMed and Embase to screen relevant studies from April 2014 to November 2021. A meta-analysis was performed to identify the association between CDI and hematopoietic transplantation based on the standard mean difference and 95% confidence intervals (CIs). Among the 431 retrieved citations, we obtained 43 eligible articles, which included 15,911 HSCT patients at risk. The overall estimated prevalence of CDI was 13.2%. The prevalence of CDI among the 10,685 allogeneic transplantation patients (15.3%) was significantly higher than that among the 3,840 autologous HSCT recipients (9.2%). Different incidence rates of CDI diagnosis over the last 7 years were found worldwide, of which North America (14.1%) was significantly higher than Europe (10.7%) but not significantly different from the prevalence among Asia (11.6%). Notably, we found that the estimated prevalence of CDI diagnosed by polymerase chain reaction (PCR) (17.7%) was significantly higher than that diagnosed by enzyme immunoassay (11.5%), indicating a significant discrepancy in the incidence rate of CDI owing to differences in the sensibility and specificity of the detection methods. Recurrence of CDI was found in approximately 15% of the initial patients with CDI. Furthermore, 20.3% of CDI cases were severe. CDI was found to be a common complication among HSCT recipients, displaying an evident increase in the morbidity of infection.

Optimized cyclosporine starting dose may reduce risk of acute GvHD after allogeneic hematopoietic cell transplantation: a single-center cohort study

Cyclosporine A (CsA) is commonly used for Graft versus Host Disease (GvHD) prophylaxis at a recommended starting dose of 3 mg/kg/d: Evidence for the effect of different CsA starting doses on GvHD risk is limited. We therefore estimated the association of 5 mg/kg/d (CsA5) and 3 mg/kg/d (CsA3) CsA starting doses with GvHD risk in two consecutive cohorts of allogeneic hematopoietic cell transplantation (allo-HCT) patients, exploring potential risk factors for incident acute GvHD, with a focus on CsA starting dose. We analyzed 519 patients within CsA5 (n = 153) and CsA3 (n = 366). The cumulative incidence function of acute GvHD grade ≥2 was higher in the CsA3 compared to the CsA5 group (41% vs. 33%, respectively; p = 0.043), without impacting chronic GvHD. In multivariable analysis, a CsA starting dose of 3 mg/kg/d, no ATG use, unrelated donor and high to very high disease risk index were significantly associated with acute GvHD grade ≥2. A higher CsA starting dose of 5 mg/kg/d was independently associated with lower acute GvHD risk, and higher CsA levels in the early period after allo-HCT were reached.

Pharmacogenomic prescribing opportunities in percutaneous coronary intervention and bone marrow transplant patients.

Aim: To evaluate the potential impact of preemptive multigene pharmacogenomic (PGx) testing on medication prescribing in real-world clinical settings. Patients & methods: Prescription frequencies for 65 medications with actionable PGx recommendations were collected in 215 percutaneous coronary intervention (PCI) and 131 allogeneic hematopoietic cell transplant (allo-HCT) patients. A simulation projected the number of PGx-guided prescribing opportunities. Results: In PCI and allo-HCT patients, respectively, 66.5 and 90.1% were prescribed at least one medication with actionable PGx prescribing recommendations. Simulations projected 26.5 and 41.2 total PGx-guided prescribing opportunities per 100 PCI and allo-HCT patients, respectively, if multigene PGx results were available. Conclusion: A multigene PGx testing strategy offers potential to optimize medication prescribing beyond clopidogrel and tacrolimus in PCI and allo-HCT patients.

Pre-transplant conditioning regimens in allogeneic transplantation for patients with aplastic anemia

Pre-transplant conditioning regimens in allogeneic transplantation for patients with aplastic anemia

Survey on delirium in allogeneic hematopoietic cell transplant patients at our hospital

Survey on delirium in allogeneic hematopoietic cell transplant patients at our hospital

Granulocyte Colony-Stimulating Factor Is Safe and Well Tolerated following Allogeneic Transplantation in Patients with Sickle Cell Disease

Granulocyte colony-stimulating factor (G-CSF) used after hematopoietic stem cell transplantation (HSCT) can enhance neutrophil recovery in patients rendered neutropenic by the preparative regimen. G-CSF is contraindicated in patients with sickle cell disease (SCD), because life-threatening complications can ensue in the presence of sickle vasculopathy. The safety profile of G-CSF after HSCT for SCD has not been described, however. We report clinical outcomes in the first 100 days post-HSCT in 62 patients supported with G-CSF until neutrophil recovery on a clinical trial of reduced- intensity conditioning HSCT for SCD. The patients received G-CSF for a median of 9 days (range, 5 to 33 days) post-transplantation from the best available stem cell source. Preparation for transplantation included a target hemoglobin S level of ≤45%. Neutrophil engraftment (absolute neutrophil count >0.5×103/mL) was achieved at a median of 13 days (range, 10 to 34 days), and platelet engraftment (>50×103/mL) was achieved at a median of 19 days (range, 12 to 71 days). The median duration of inpatient hospitalization following stem cell infusion (day 0) was 21.5 days (range, 11 to 33 days). No patient developed SCD-related complications following G-CSF use. The most common organ toxicities encountered between G-CSF initiation (on day +7) and day +100 were anorexia (n=14), hypertension (n=11), and electrolyte imbalance requiring correction (n=9). Central nervous system-related events were noted in 5 patients, all of whom had preexisting cerebral vasculopathy/moyamoya disease, attributed to reversible posterior leukoencephalopathy syndrome in the presence of calcineurin inhibitor therapy and hypertension. We conclude that G-CSF does not adversely impact SCD HSCT recipients and can be safely used post-transplantation to enhance neutrophil recovery.

Frequency and Risk Factors of Cyclosporine-Induced Neurotoxicity in Allogeneic Stem Cell Transplant Recipients.

Background and objectiveThe calcineurin inhibitor cyclosporine A is routinely used for prophylaxis against graft-versus-host-disease (GvHD) in human leukocyte antigen (HLA)-matched allogeneic stem-cell transplant patients and is a major etiological factor for neuropathological symptoms that are reversible in most cases. In this study, we aimed to determine the frequency and risk factors of cyclosporine-induced neurotoxicity (CIN) in HLA-matched allogeneic stem cell transplant patients.MethodsThe study spanned the period from January 2016 to December 2019. Consecutive HLA-matched allogeneic stem-cell transplant patients of all ages were included in the study. Descriptive and risk factor analyses for the development of CIN with respect to age, sex, primary diagnosis, conditioning regimen, electrolyte abnormalities, and cyclosporine trough levels during the neurological episode were performed.ResultsA total of 106 HLA-matched patients with a median age of 6.3 years [interquartile range (IQR): 0.5-46 years], of which 37 (35%) were females, were included in the study. The mean cyclosporine trough level was 500 ±286 mg/dl. Neurological symptoms were found in 27 (26%) patients. A total of 14 (13%) patients were diagnosed with CIN. The frequency of other neurological symptoms included headache in 46 (43%), disorientation in 17 (16%), seizures in 12 (11%), visual disturbance in 11 (10%), and aphasia in seven (7%) patients. Posterior reversible encephalopathy syndrome (PRES) was found in six (6%) patients. All patients with CIN had hypertension and none had a fever. Multivariate logistic analysis showed that the presence of seizures [odds ratio (OR): 10.0, p<0.001] and the absence of fever (OR: 0.02, p<0.001) were associated with the diagnosis of CIN.ConclusionThe prevalence of CIN is not uncommon (13%) in patients receiving cyclosporine for GvHD prophylaxis. Neurological complications, especially seizures, are common in CIN, and fever might indicate an alternative diagnosis. Prompt recognition of neurological signs and symptoms and early intervention can halt the progression of the disease.

GITMO Registry Study on Allogeneic Transplantation in Patients Aged ≥60 Years from 2000 to 2017: Improvements and Criticisms

Today, allogeneic stem cell transplantation (allo-SCT) can be offered to patients up to age 70 to 72 years and represents one of the most effective curative treatments for many hematologic malignancies. The primary objective of the study was to collect data from the allo-SCTs performed in Italy between 2000 and 2017 in patients aged ≥60 years to evaluate the changes in safety and efficacy outcomes, as well as their distribution and characteristics over time. The Italian Group for Bone Marrow Transplantation, Hematopoietic Stem Cells and Cell Therapy (GITMO) AlloEld study (ClinicalTrials.gov identifier NCT04469985) is a retrospective analysis of allo-SCTs performed at 30 Italian transplantation centers in older patients (age ≥60 years) between 2000 and 2017 (n=1996). For the purpose of this analysis, patients were grouped into 3 time periods: time A, 2000 to 2005 (n=256; 12%); time B, 2006 to 2011 (n=584; 29%); and time C, 2012 to 2017 (n=1156; 59%). After a median follow-up of 5.6 years, the 5-year nonrelapse mortality (NRM) remained stable (time A, 32.8%; time B, 36.2%; and time C, 35.0%; P=.5), overall survival improved (time A, 28.4%; time B, 31.8%; and time C, 37.3%; P=.012), and the cumulative incidence of relapse was reduced (time A, 45.3%; time B, 38.2%; time C, 30.0%; P < .0001). The 2-year incidence of extensive chronic graft-versus-host disease was reduced significantly (time A, 17.2%; time B, 15.8%; time C, 12.2%; P=.004). Considering times A and B together (2000 to 2011), the 2-year NRM was positively correlated with the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) score; NRM was 25.2% in patients with an HCT-CI score of 0, 33.9% in those with a score of 1 or 2, and 36.1% in those with a score of 3 (P < .001). However, after 2012, the HCT-CI score was not significantly predictive of NRM. This study shows that the transplantation procedure in elderly patients became more effective over time. Relapse incidence remains the major problem, and strategies to prevent it are currently under investigation (eg, post-transplantation maintenance). The selection of patients aged ≥60 could be improved by combining HCT-CI and frailty assessment to better predict NRM.

Comparison of Outcomes After Second Allogeneic Hematopoietic Cell Transplantation Versus Donor Lymphocyte Infusion in Allogeneic Hematopoietic Cell Transplant Patients

BackgroundAllogeneic hematopoietic cell transplantation (HCT) is potentially curative for hematological disease however can be complicated by relapse or graft failure (GF), for which second-HCT and donor lymphocyte infusions (DLI) are performed. This study aimed to compare outcomes following the two interventions. MethodsWe retrospectively investigated 89 patients with relapse or GF after first-HCT, 50 (56%) underwent second HCT and 39 (44%) received (DLI), from June 2011 to September 2020. ResultsMedian age at intervention was 55 years (19-72). Second-HCT was performed for relapse in 19 patients and for GF in 31 patients (primary GF in 11 and secondary in 20 patients), same donor was used in 25 (50%) patients. DLI was performed for relapse in 20 and for secondary GF in 19 patients. Median number of DLI administered was 2 (range 1-11). Univariate analysis demonstrated 2 year overall survival (OS) for second-HCT was superior when performed for relapse (65%) compared to GF (44%) (P = .03). For DLI patients, 2 year OS was 49% for GF and 45% for relapse patients (P = .49). For relapse as an indication, second-HCT demonstrated borderline superiority compared to DLI (P = .07). Multivariable analysis demonstrated for OS for the entire cohort demonstrated donor mismatch (HR 0.50, 95% CI 0.26%-0.94%, P = .03), KPS at time of intervention (HR 2.10, 95% CI 1.14%-3.85%, P = .02) and time from first-HCT to intervention (HR 0.51, 95% CI 0.28%-0.93%, P = .03) as significant variables. ConclusionSecond-HCT may improve outcomes when performed for relapse post-transplant if patients achieve remission again, while DLI may be reserved for patients with active disease.

Effect of Age on Outcomes of Allogeneic Transplantation in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

Background: Allogeneic stem cell transplantation (allo-SCT) has become an increasingly important consolidation treatment option for patients with acute myeloid leukemia (AML) and as upfront therapy for patients with high-risk myelodysplastic syndrome (MDS). Although the median age at diagnosis for both diseases is above 65 years, studies evaluating allo-SCT as treatment option for patients aged 65 years or older are limited. Further, as the population ages, the number of patients above 65 years considered for allo-SCT will continue to rise. Thus, the aim of our current investigation was to analyze outcomes based on age in AML/MDS patients <65 years old and ≥65 years old who received allo-SCT at the Ohio State University.Methods: A retrospective analysis was performed for all AML/MDS patients who received allo-SCT between January 1984 and December 2018 at our institution. Primary endpoints included progression free survival (PFS) and overall survival (OS). PFS was counted from the day of transplantation to relapse or death. OS was defined as survival from the day of allo-SCT until death from any cause, with censoring of patients known to be alive at the time of last follow-up. PFS and OS were calculated using Kaplan Meier Curves. Secondary endpoints included cumulative incidences of grade II-IV and III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, and non-relapse mortality (NRM). Cumulative incidence rates of aGVHD, cGVHD, relapse, NRM were estimated and compared using Gray's test accounting for competing risks.Results: The cohort consisted of 900 AML/MDS patients, with 150 patients ≥65 years and 750 patients <65 years. The median age at transplant for the <65 years group was 49 years (range: 18-64 years) and 68 years (range: 65-76 years) for the ≥65 years group. Gender, race, Karnofsky score, and comorbidity index were similar between the two groups. A higher proportion of patients received myeloablative (MA) conditioning (65.1%) in the <65 years of age compared to 20% in the ≥65 years of age (p<0.01). A higher proportion of older patients had matched unrelated donors (57.3%), and reduced intensity conditioning (RIC) regimens (80%).The median time from diagnosis to transplantation was 176 days (range: 55-4920) for age <65 years and 168 days (range: 34-6079 days) for age ≥65 years. Median follow-up from allo-SCT was 5.9 years (range 0.8-35.9 years) and 3.4 years (range: 1.0-9.6 years) from transplantation among survivors. Neutrophil and platelet engraftment were similar among the groups (p=0.35; 0.11). 3 year OS of 42.3% (95% CI: 38.7-45.8%) and PFS of 38.3% (95% CI: 34.8%-41.9%) were observed for age <65 years. The corresponding OS and PFS for age ≥65 years was 46.3% (95% CI: 37.9%-54.3%) and 43.0% (95% CI: 34.7%-51.0%), respectively (Figure 1a & 1b). Cumulative incidences of relapse at 1 year in <65 and ≥65 years were 26.4% and 25.3%, respectively (p=0.43). The cumulative incidence of NRM at 1 year in <65 and ≥65 years was 23.2% and 17.3%, respectively (p=0.12; Figures 1c and d). The incidences of acute and chronic GVHD were similar in the two age groups. The cumulative incidence of aGVHD at day 100 in <65 and ≥65 years was 40.3% (95% CI: 36.4%-44.2%) and 43.0% (95% CI: 34.9%-50.7%), respectively. The cumulative incidence of cGVHD at day 365 in <65 and ≥65 years was 40.8% (95% CI: 36.9%-44.6%) and 41.6% (95% CI: 33.6%-49.4%), respectively.Conclusion: Overall, our study suggests similar outcomes for elderly patients undergoing allo-HCT as compared to their counterparts, which is in line with prior studies. This likely is due to advancements in the transplant field, including the development of RIC and alternative donors, which have allowed greater access to transplant for older adults. Utilization of allo-HCT is feasible and should be considered for AML/MDS patients ≥65 years. Further research is underway to evaluate the important determinants of health status in older patients undergoing allo-HCT and to ultimately help predict NRM (BMT CTN 1704). [Display omitted] DisclosuresBumma: Amgen, Sanofi: Speakers Bureau; Janssen, Oncopeptides, Sanofi: Consultancy. Vasu: Seattle Genetics: Other: travel support; Boehringer Ingelheim: Other: Travel support; Kiadis, Inc.: Research Funding; Omeros, Inc.: Membership on an entity's Board of Directors or advisory committees. Jaglowski: Takeda: Consultancy; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; CRISPR Therapeutics: Consultancy; Novartis: Consultancy, Research Funding. Mims: Syndax Pharmaceuticals: Consultancy; BMS: Consultancy; Jazz Pharmaceuticals: Consultancy; Abbvie: Consultancy; Genentech: Consultancy; Kura Oncology: Consultancy; Leukemia and Lymphoma Society: Consultancy; Glycomemetics: Research Funding; Aptevo: Research Funding; Xencor: Research Funding; Daiichi-Saynko: Consultancy. Brammer: Celgene: Research Funding; Seattle Genetics: Speakers Bureau; Kymera Therapeutics: Consultancy. Saad: Incyte Pharmaceuticals: Consultancy; careDx: Consultancy; Amgen: Research Funding; Kadmon: Research Funding; OrcaBio: Research Funding; Magenta Therapeutics: Consultancy. de Lima: Miltenyi Biotec: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.