Relapse after Allogeneic Hematopoietic Cell Transplantation for Multiple Myeloma: Survival Outcomes and Factors Influencing Them.

Many patients with multiple myeloma (MM) eventually relapse even after allogeneic hematopoietic cell transplantation (alloHCT) for curative intent. Over the past decade, outcomes for patients with MM have improved significantly with the availability of new therapies, including next-generation proteasome inhibitors, immunomodulatory agents, and, more recently, monoclonal antibodies. Although several published studies have evaluated the outcomes of alloHCT for MM, the data on survival outcomes in patients with MM experiencing disease relapse following alloHCT are limited. In addition, the predictors for postrelapse survival in these patients are not known. In this study, we examined the outcomes of a single-center cohort of 60 patients with MM who experienced relapse or progression after alloHCT. In addition, we evaluated the use of salvage regimens for treatment of relapsed MM and analyzed the predictors for improved postrelapse survival. After a median follow-up of 2.2 years from the time of relapse, the median duration of postrelapse survival was 1.8 years (95% confidence interval [CI], 1.2 to 5.0 years). Patients received a median of 3 lines of therapy (range, 0 to 10) for treatment of MM beyond the post-alloHCT relapse/progression. Multivariate analysis identified cytogenetic risk (standard risk versus high risk; hazard ratio [HR], .34; P = .01), time to relapse after alloHCT (>12 months versus ≤12 months: HR, .41; P = .04), and occurrence of acute graft-versus-host disease (GVHD) before relapse (GVHD versus no GVHD: HR, 2.89; P = .01) significantly affected postrelapse survival. These data illustrate that long-term myeloma control and survival is attainable in those relapsing/progressing after alloHCT and suggest that the synergism between novel therapies and the allogeneic immune platform is the key to improved survival in this high-risk patient population.

Propylene Glycol-Free Melphalan versus PG-Melphalan as Conditioning for Autologous Hematopoietic Cell Transplantation for Myeloma.

High-dose melphalan (Mel) conditioning before autologous hematopoietic cell transplantation (autoHCT) is standard of care for patients with transplantation-eligible multiple myeloma. The traditional lyophilized Mel formulation has inadequate solubility and stability after reconstitution, leading to the use of propylene glycol (PG) as a solubilizing agent. A newer PG-free Mel preparation (Evomela) uses beta cyclodextrin captisol as a solubilizing agent and was approved by the United States Food and Drug Administration as a conditioning agent based on a single-phase IIb study showing bioequivalence. We compared the outcomes of consecutive patients with myeloma undergoing autoHCT using the 2 formulations of Mel for conditioning as our center switched from using the older formulation (PG-Mel) to the newer one (PGF-Mel). Of 294 autoHCT recipients, 162 received PG-Mel conditioning and 132 received PGF-Mel conditioning. The PGF-Mel group was older and had a lower average Karnofsky Performance Status score. PGF-Mel was associated with faster neutrophil recovery (median, 12 days versus 13 days; P < .001), fewer grade 3-4 infections within 30 days of autoHCT (1.5% versus 8.0%; P = .048), and a lower 30-day rehospitalization rate (6.8% versus 17.9%; P = .04), as confirmed by propensity-weighted analysis. No significant between-group differences were detected in mucositis, organ toxicity, myeloma response, or 100-day mortality.

Utilization and Cost Implications of Hematopoietic Progenitor Cells Stored for a Future Salvage Autologous Transplantation or Stem Cell Boost in Myeloma Patients.

Autologous hematopoietic cell transplantation (autoHCT) is a standard initial treatment for multiple myeloma (MM). Consensus guidelines recommend collecting sufficient hematopoietic progenitor cells (HPCs) for 2 autoHCTs in all eligible patients. Despite a lack of published data on the utilization of HPCs stored for future use, it is common practice across transplantation programs to collect enough HPCs for 2 autoHCTs in MM patients. In this single-center retrospective study, we analyzed the utilization of HPCs collected and stored at the time of first autoHCT in patients with MM, along with the cost implications of HPC collection targets sufficient for 2 transplantations. In a cohort of 400 patients (median age, 63 years; range, 22 to 79 years), after a median follow-up of 50.4 months, 197 patients had relapsed and 36 had received HPC infusion as salvage autoHCT (n = 29) and/or HPC boost (n = 8). In this cohort, a median CD34+ cell dose of 4.3 × 106/kg (range, 1.1 to 12.94.3 × 106/kg) was used for first autoHCT, and a median of 4.4 × 106/kg (range, 1.0 to 20.2× 106/kg) CD34+ cells were stored for future use. At 6 years after the first autoHCT, the estimated cumulative incidence of salvage autoHCT was 12.0% without HPC boost and 13.9% with HPC boost. HPC utilization was significantly higher in the 60- to 64-year age group, whereas no patients who were age ≥70 years at the time of first autoHCT received salvage autoHCT. Using the CD34+ cell dose infused during the first autoHCT as the cutoff for individual patients, the estimated mean additional cost of HPC collection intended for subsequent use (over and above the HPCs used for first autoHCT) was $10,795 ($4.32 million for the entire cohort), an estimated 14% of which (ie, $583,600) was actually used up in salvage autoHCT by 6 years from first autoHCT. In conclusion, our results suggest the need for reappraisal of HPC collection targets for salvage autoHCT and argue against HPC collection and storage for salvage autoHCT in patients age ≥70 years at the time of first autoHCT.

Fludarabine/Busulfan Conditioning-Based Allogeneic Hematopoietic Cell Transplantation for Myelofibrosis: Role of Ruxolitinib in Improving Survival Outcomes.

Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative treatment modality for primary myelofibrosis (MF) and related myeloproliferative neoplasms. Older age at diagnosis and age-related comorbidities make most patients ineligible for allo-HCT, given concerns for nonrelapse mortality (NRM). Here we report the outcomes of 37 consecutive recipients of allo-HCT for MF performed at a single center between 2009 and 2018 with a standardized institutional protocol. Most patients received ruxolitinib before HCT (n = 32), and those with splenomegaly >22 cm received pretransplantation splenic irradiation. The median age at HCT was 60 years (range, 40 to 74 years), and 68% of the cohort carried a JAK2 driver mutation. All patients received fludarabine/busulfan-based conditioning; 22 patients (59%) received a reduced-intensity conditioning regimen. All patients received peripheral blood grafts, from a matched sibling donor in 16 patients (43%), an unrelated donor in 20 patients, and a haploidentical-related donor in 1 patient. Sixty-one percent had a Hematopoietic Cell Transplantation Comorbidity Index ≥3, 40% had a Karnofsky Performance Status score <90, and 24% had a high-risk DIPSS Plus score. With a median follow-up of 40.2 months (range, 16.9 to 115 months), the 3-year overall survival and relapse-free survival were 81.1% (95% confidence interval [CI], 64.4% to 90.5%) and 78.4% (95% CI, 61.4% to 88.5%), respectively. Only 2 patients relapsed/progressed after transplant. NRM at 2 years was 16.2% (95% CI, 6.5% to 29.9%). All patients engrafted. Sixteen patients were treated with ruxolitinib post-transplantation for graft-versus-host disease, graft rejection/relapse, or persistent MF. These results suggest that pretransplantation ruxolitinib, fludarabine/busulfan-based conditioning, and splenic management are keys to improved transplantation outcomes in patients undergoing allo-HCT for MF.

Severity of Cytokine Release Syndrome and Its Association with Infections after T Cell-Replete Haploidentical Related Donor Transplantation.

An increased risk of infections has been described after T cell-replete haploidentical cell transplantation (haploHCT). Cytokine release syndrome (CRS) after haploHCT is a known phenomenon, but the impact of CRS severity on the risk of infections remains unexplored. We retrospectively evaluated 78 consecutive adult haploHCT recipients from 2012 to 2018 for the development of CRS (graded based on the criteria of Lee et al) and examined the incidence and mortality due to infections in correlation with CRS severity. In our study cohort, which was stratified into 3 groups by severity of CRS, 80% of the patients developed infections within 180 days of HCT. Significantly higher proportions of patients with CRS grade 2 (89%) and grade ≥3 (90%) than patients with CRS grade 0-1 (68%) had at least 1 infection in the first 100 days (P = .04). Bloodstream infections (BSIs) were seen more frequently in patients with CRS grade 2 and grade ≥3 in the first 6 months. Multivariable analysis for time to infection showed that CRS grade ≥3 was independently associated with an elevated risk of any infection compared with CRS grade 0-1 (hazard ratio [HR], 3.05; P = .007). CRS grade ≥3 was also associated with a higher hazard of viral (HR, 3.42; P = .04) and bacterial infections (HR, 2.83; P = .03) compared with CRS grade 0-1. After adjusting for time to neutrophil engraftment as a time-dependent covariate, CRS grade ≥3 still had a significant effect on viral infections (HR, 2.49; P = .03), but not on bacterial infections (HR, 1.32; P = .57). CRS grade was also a significant predictor for infection density (overall, bacterial, and viral). The incidence of infection-related mortality by day +100 was higher in patients with severe CRS. Severe CRS developing after post-transplantation cyclophosphamide-based haploHCT is independently associated with viral infections and an increased risk of bacterial infections, likely through delayed neutrophil engraftment.

Ixazomib for Chronic Graft-versus-Host Disease Prophylaxis following Allogeneic Hematopoietic Cell Transplantation.

Chronic graft-versus-host disease (cGVHD) is major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Ixazomib is an oral, second-generation, proteasome inhibitor that has been shown in preclinical models to prevent GVHD. We conducted a phase I/II trial in 57 patients to evaluate the safety and efficacy of ixazomib administration for cGVHD prophylaxis in patients undergoing allogeneic HCT. Oral ixazomib was administered on a weekly basis for a total of 4 doses, beginning days +60 through +90, to recipients of matched related donor (MRD, n = 25) or matched unrelated donor (MUD, n = 26) allogeneic HCT in phase II portion of the study, once the recommended phase II dose of 4 mg was identified in phase I (n = 6). All patients received peripheral blood graft and standard GVHD prophylaxis of tacrolimus and methotrexate. Ixazomib administration was safe and well tolerated, with thrombocytopenia, leukopenia, gastrointestinal complaints, and fatigue the most common adverse events (>10%). In phase II (n = 51), the cumulative incidence of cGVHD at 1 year was 36% (95% confidence interval [CI], 19% to 54%) in the MRD cohort and 39% (95% CI, 21% to 56%) in the MUD cohort. One-year cumulative incidence of nonrelapse mortality (NRM) and relapse was 0% and 20% (95% CI, 8% to 36%) in the MRD cohort, respectively. In the MUD cohort, the respective NRM and relapse rates were 4% (0% to 16%) and 34% (17% to 52%). The outcomes on the study were compared post hoc with contemporaneous matched Center for International Blood and Marrow Transplant Research (CIBMTR) controls. This post hoc analysis showed no significant improvement in cGVHD rates in both the MRD (hazard ratio [HR] = 0.85, P = .64) or MUD cohorts (HR = 0.68, P = .26) on the study compared with CIBMTR controls. B cell activating factor plasma levels were significantly higher after ixazomib dosing in those who remained cGVHD free compared with those developed cGVHD. This study shows that the novel strategy of short-course oral ixazomib following allogeneic HCT is safe but did not demonstrate significant improvement in cGVHD incidence in recipients of MRD and MUD transplantation compared with matched CIBMTR controls. This study is registered at www.clinicaltrials.gov as NCT02250300.

Efficacy, Toxicity, and Infectious Complications in Ruxolitinib-Treated Patients with Corticosteroid-Refractory Graft-versus-Host Disease after Hematopoietic Cell Transplantation.

Corticosteroid-refractory graft-versus-host disease (SR-GVHD) remains a significant source of morbidity after allogeneic hematopoietic cell transplantation. No standard therapy exists in this setting; however, recent studies have demonstrated a very promising role for ruxolitinib, an oral Janus kinase 1/2 inhibitor. With increasing evidence of efficacy for SR-GVHD, limited data exist describing complications of ruxolitinib use, specifically infectious complications during use in SR-GVHD. In this study we report outcomes and infectious complications at our institution with ruxolitinib use. Overall, 43 patients were treated with ruxolitinib for SR-GVHD, 19 for acute SR-GVHD and 24 for chronic SR-GVHD. With respect to acute SR-GVHD, 15 patients had grade III acute GVHD and 4 patients had grade IV acute GVHD. At 28 days, a response rate of 84% was detected. With respect to chronic SR-GVHD, 16 patients had moderate refractory disease and 8 had severe refractory disease. At around 28 days, a 63% response rate was detected. Overall, 42% of patients (n = 18) treated with ruxolitinib had a documented infectious event. Infectious events were significantly more common among patients treated for acute SR-GVHD (P < .005). Among patients treated for acute SR-GVHD, both viral (n = 11) and bacterial (n = 10) events were frequently encountered. Cytomegalovirus reactivation was detected in 4 patients without organ involvement in any patient. Bacteremia was the most common bacterial event (n = 8), and 2 patients died after development of bacteremia. Only 5 of 24 patients treated with ruxolitinib for chronic SR-GVHD developed infectious complications after initiation of therapy. Nearly an even number of viral (n = 3) and bacterial (n = 4) were detected. This study supports the use of ruxolitinib in SR-GVHD, with impressive responses observed in both acute and chronic SR-GVHD. Infectious complications were particularly frequent among patients treated for acute SR-GVHD, and nearly all these patients were concurrently on high-dose steroids while on ruxolitinib. This study suggests careful monitoring for viral reactivation is required for patients initiated on ruxolitinib, supports the role of continuing prophylactic antimicrobial measures in ruxolitinib-treated GVHD patients, and raises the question of whether bacterial prophylaxis should be considered among patients initiated on ruxolitinib for acute SR-GVHD, particularly while on high-dose steroids.

Direct HLA Genetic Comparisons Identify Highly Matched Unrelated Donor-Recipient Pairs with Improved Transplantation Outcome.

HLA matching by allele-level genotyping is largely based on genetic similarity between a few exons that encode the antigen recognition domain (ARD) of the HLA protein. Next-generation sequencing (NGS) can identify HLA genetic polymorphisms in non-ARD-encoding exons, introns, and untranslated regions, but the impact of these polymorphisms on hematopoietic cell transplantation (HCT) outcome is unclear. We performed NGS-based sequencing of 11 HLA loci on a well-characterized retrospective cohort of 166 unrelated donor-recipient HCT pairs. Genetic differences between HCT pairs were identified and visualized using a novel bioinformatics approach that directly compares phased full-length HLA sequences. Our approach was able to correctly classify HCT pairs without known HLA allele-level mismatches and also to identify a subset of HLA allele-matched HCT pairs with very few to no genetic differences in the sequenced HLA regions. This highly HLA genetically matched unrelated HCT group shows improved overall survival and reduced acute graft-versus-host disease compared with HCT pairs with HLA allele-level mismatches. These results suggest that direct genetic matching of HLA loci may offer an additional means of HCT donor selection beyond traditional HLA allele comparisons and suggests that genetic similarity as defined by HLA sequencing may have a novel role in unrelated HCT donor selection. Finally, our approach can enable larger cohort studies with adequate power to detect differences in other HCT outcomes based on genetic similarity within the HLA loci.

Peripheral Blood Grafts for T Cell-Replete Haploidentical Transplantation Increase the Incidence and Severity of Cytokine Release Syndrome.

T cell-replete post-transplant cyclophosphamide (PTCy)-based protocols have led to increasing use of haploidentical allogeneic hematopoietic cell transplantation (haploHCT). With this approach, bidirectional alloreactivity causing nonengraftment or severe graft-versus-host disease (GVHD) is no a longer major barrier to haploHCT. PTCy eliminates alloreactive lymphocytes but spares CD34+ stem cells and regulatory T lymphocytes, resulting in reliable hematopoietic recovery with relatively low incidence of GVHD. The immediate post-haploHCT course, usually before PTCy administration, is often complicated by cytokine release syndrome (CRS). The predictors of CRS and its effect on outcomes post-transplant have not been fully ascertained. We analyzed the outcomes of 66 patients who received haploHCT at our institution. Using published CRS criteria we identified 48 patients who developed CRS. In multivariate analysis peripheral blood grafts were significantly associated with grade ≥ 2 CRS, compared with bone marrow. Grade ≥ 2 CRS (compared with grade < 2) was not associated with differences in overall survival or nonrelapse mortality. Severe CRS was associated with a statistically nonsignificant trend toward higher incidences of grades III to IV acute GVHD, especially in the context of peripheral blood grafts. CRS is a common complication after T cell-replete peripheral blood haploHCT, but post-transplant survival outcomes may not be affected in those with severe CRS.

Evaluating Antibiotic De-escalation for Autologous Stem Cell Transplant Patients With Febrile Neutropenia in a Real-World Clinical Setting.

Febrile neutropenia (FN) is a complication in approximately 90% of autologous stem cell transplant (SCT) patients. Guidelines support early broad-spectrum antibiotics (BSA) to prevent morbidity and mortality. However, in patients who are clinically stable and deemed to have a fever of unknown origin, the optimal duration of BSA is unknown. Accumulating evidence suggests that de-escalation of BSA in select patients may decrease duration of BSA exposure without compromising clinical outcomes such as infection, recurrent fever, and readmission. With this, a de-escalation protocol was implemented at Vanderbilt University Medical Center (VUMC) to identify autologous SCT patients who may benefit from early de-escalation of BSA. The objectives of this study were to analyze the impact of early empiric antibiotic de-escalation on the duration of BSA as well as its impact on the incidence of recurrent fever and documented infection in autologous SCT patients. This was a single-center, retrospective study evaluating patients older than 18 years of age who underwent autologous SCT and experienced an episode of FN from January 2018 to December 2022 at VUMC (N = 195). The protocol was initiated on January 1, 2020, to de-escalate BSA back to prophylaxis in stable neutropenic patients determined to have a fever of unknown origin. The primary outcome was the number of BSA days within 30 days. Secondary clinical outcomes included recurrent fever, documented infection, readmission, 30-day mortality, and 90-day non-relapsed mortality (NRM). Outcomes were compared across pre- and postprotocol groups with a Wilcoxon rank sum test, Pearson chi-square test, or regression analysis as appropriate. The median BSA duration was 4.7 and 2.7 days in the pre- and postprotocol groups, respectively (P < .001). Recurrent fever (14.2% versus 16.0%, P = .726), documented infection (1.7% versus 6.7%, P = .068), and readmission (13.3% versus 22.7%, P = .091) within 30 days were not significantly different between the two groups. Neither 30-day mortality (0.8% versus 1.3%, P = .736) nor 90-day NRM (0.8% versus 1.3%, P = .736) differed. The implementation of an early de-escalation protocol for autologous SCT patients who develop FN was associated with a reduction in duration of BSA compared to the preprotocol group without a significant difference in readmission, recurrent fevers, and documented infections. This study adds to existing evidence that early de-escalation of BSA in FN patients with a fever of unknown origin who are afebrile and clinically stable is safe and reduces unnecessary antibiotic use.

Severity and organ distribution of chronic graft-versus-host disease with posttransplant cyclophosphamide-based versus methotrexate/calcineurin inhibitor-based allogeneic hematopoietic cell transplantation.

The reduced risk of chronic graft-versus-host-disease (GVHD) with posttransplant cyclophosphamide (ptCy) in the setting of haploidentical related donor and more recently, with HLA-matched related and matched and mismatched unrelated donor allogeneic transplantation has been established. There is, however, paucity of data to show if ptCy impacts chronic GVHD pathogenesis, its phenotype and evolution after HCT regardless of the donor status. We examined the differences in chronic GVHD incidence and presentation in 314 consecutive patients after receiving their first allogeneic transplantation (HCT) using ptCy-based GVHD prophylaxis (ptCy-HCT; n = 120; including 95 with haploidentical related donor) versus conventional calcineurin inhibitor-based prophylaxis (CNI-MUD; n = 194) between 2012 and 2019. The 1-year cumulative incidence of all-grade chronic GVHD and moderate/severe chronic GVHD was 24% and 12%, respectively, after ptCy-HCT and 40% and 23% in the CNI-MUD recipients (p = 0.0003 and 0.007). Multivariable analysis confirmed that use of CNI-based GVHD prophylaxis and peripheral blood stem cell graft as the risk factors for chronic GVHD. The cumulative incidence of visceral (involving ≥1 of the following organs: liver, lungs, gastrointestinal tract, serous membranes) chronic GVHD was significantly higher with CNI-MUD vs. ptCy-HCT (27% vs. 15% at 1 year, p = 0.009). The incidence of moderate/severe visceral chronic GVHD was 20% in CNI-MUD group vs. 7.7% in the ptCy-HCT group at 1 year (p = 0.002). In addition, significantly fewer ptCy-HCT recipients developed severe chronic GVHD in ≥3 organs (0.8%) vs. 8.8% in the CNI-MUD group at 1-year posttransplant (p = 0.004). There was no significant different in relapse, non-relapse mortality, and relapse-free and overall survival between the two groups. Further investigation is needed to confirm that reduced risk and severity of chronic GVHD, less visceral organ distribution with ptCy-HCT leads to improved quality of life.

Stem Cell Mobilization Yields with Daratumumab- and Lenalidomide-Containing Quadruplet Induction Therapy in Newly Diagnosed Multiple Myeloma: Findings from the MASTER and GRIFFIN Trials.

For eligible patients with newly diagnosed multiple myeloma (NDMM), standard of care includes induction therapy followed by autologous stem cell transplantation (ASCT). Daratumumab as monotherapy and in combination treatment is approved across multiple lines of therapy for multiple myeloma (MM), and lenalidomide is an effective and commonly used agent for induction and maintenance therapy in MM. However, there is concern that lenalidomide and daratumumab given as induction therapy might impair mobilization of stem cells for ASCT. Therefore, we assessed stem cell mobilization in patients following frontline induction therapy in the MASTER and GRIFFIN phase 2 clinical studies by examining stem cell mobilization yields, apheresis attempts, and engraftment outcomes for patients from each study. Adult transplantation-eligible patients with NDMM received induction therapy consisting of daratumumab plus carfilzomib/lenalidomide/dexamethasone (D-KRd) for four 28-day cycles in the single-arm MASTER trial or lenalidomide/bortezomib/dexamethasone (RVd) with or without daratumumab (D) for four 21-day cycles in the randomized GRIFFIN trial, followed by stem cell mobilization and ASCT in both studies. Institutional practice differed regarding plerixafor use for stem cell mobilization; the strategies were upfront (ie, planned plerixafor use) or rescue (ie, plerixafor use only after mobilization parameters indicated failure with granulocyte colony-stimulating factor [G-CSF] alone). Descriptive analyses were used to summarize patient characteristics, stem cell mobilization yields, and engraftment outcomes. In MASTER, 116 D-KRd recipients underwent stem cell mobilization and collection at a median of 24 days after completing induction therapy. In GRIFFIN, 175 patients (D-RVd, n = 95; RVd, n = 80) underwent mobilization at a median of 27 days after completing D-RVd induction therapy and 24 days after completing RVd induction therapy. Among those who underwent mobilization and collection, 7% (8 of 116) of D-KRd recipients, 2% (2 of 95) of D-RVd recipients, and 6% (5 of 80) of RVd recipients did not meet the center-specific minimally required CD34+ cell yield in the first mobilization attempt; however, nearly all collected sufficient stem cells for ASCT on remobilization. Among patients who underwent mobilization, plerixafor use, either upfront or as a rescue strategy, was higher in patients receiving D-KRd (97%; 112 of 116) and D-RVd (72%; 68 of 95) compared with those receiving RVd (55%; 44 of 80). The median total CD34+ cell collection was 6.0 × 106/kg (range, 2.2 to 13.9 × 106/kg) after D-KRd induction, 8.3 × 106/kg (range, 2.6 to 33.0 × 106/kg) after D-RVd induction, and 9.4 × 106/kg (range, 4.1 to 28.7 × 106/kg) after RVd induction; the median days for collection were 2, 2, and 1, respectively. Among patients who underwent mobilization, 98% (114 of 116) of D-KRd patients, 99% (94 of 95) of D-RVd patients, and 98% (78 of 80) of RVd patients underwent ASCT using median CD34+ cell doses of 3.2 × 106/kg, 4.2 × 106/kg, and 4.8 × 106/kg, respectively. The median time to neutrophil recovery was 12 days in all 3 treatment groups across the 2 trials. Because both trials used different criteria to define platelet recovery, data on platelet engraftment using the same criteria are not available. Four cycles of daratumumab- and lenalidomide-based quadruplet induction therapy had a minimal impact on stem cell mobilization and allowed predictable stem cell harvesting and engraftment in all patients who underwent ASCT. Upfront plerixafor strategy may be considered, but many patients were successfully collected with the use of G-CSF alone or rescue plerixafor.

Lifitegrast ophthalmic solution for treatment of ocular chronic graft-versus-host disease.

Ocular chronic graft-versus-host disease (oGVHD) is a relatively common complication that occurs following allogeneic hematopoietic cell transplantation. Keratoconjunctivitis sicca (KCS) is the most common manifestation of oGVHD. Lifitegrast is a lymphocyte function-associated antigen-1 antagonist approved to reduce inflammation and symptoms in patients with dry eye disease. We evaluated the efficacy and safety of lifitegrast (5% ophthalmic solution) in patients with ocular GVHD in a single-institution retrospective cohort study of eighteen allogeneic transplant recipients who received topical lifitegrast for oGVHD treatment. The outcome of interest was improvement in oGVHD severity score by National Institutes of Health (NIH) criteria. Lifitegrast was well-tolerated and no serious adverse events were observed. Lifitegrast significantly improved NIH severity scores in 8 (44%) patients. The findings of this study suggest lifitegrast is safe, well-tolerated and is an effective option for oGVHD manifesting as KCS. Prospective evaluation is warranted to confirm efficacy of lifitegrast in this population.HighlightsIn this single-institution retrospective cohort study of eighteen patients who received allogeneic transplant between 2013 and 2018, and received topical lifitegrast for treatment of ocular GVHD, the results demonstrate that lifitegrast eye drops were well-tolerated and led to improvement in symptoms of KCS in 8 (44%) patients.Lifitegrast has the potential to fulfill an unmet need in allogeneic transplant patients with ocular GVHD. Further prospective study is warranted for confirmation.

Incidence and characteristics of engraftment syndrome after autologous hematopoietic cell transplantation in light chain amyloidosis.

Engraftment syndrome (ES), a complication of autologous hematopoietic cell transplantation (auto-HCT), can occur around the time of neutrophil recovery. We sought to identify the incidence of ES in light chain (AL) amyloidosis patients undergoing auto-HCT at our centre by evaluating 72 consecutive amyloidosis patients transplanted between 1999 and 2017. To assess trends in ES over time, patients were divided into two Eras (Era 1 = 1999-2008 and Era 2 = 2009-2017) based on year of auto-HCT. Twenty-two (31%) patients developed ES; three (16%) and 19 (36%) in Era 1 and 2, respectively (p = .1). Three (16%) and 51 (96%) patients in Era 1 and 2 received chemotherapy before auto-HCT (p = <.001). The most common symptoms observed with ES in addition to fever was diarrhoea (73%), rash (68%), weight gain (56%) and non-cardiogenic pulmonary oedema (23%). Day 100 post-auto-HCT haematological response (19.5% vs. 14%, p = .7) or post-transplant best organ response (23% vs. 36%, p = .2) were not significantly different in patients who did not or did develop ES, respectively. In this single centre series, we define the incidence and characteristics of ES in AL amyloidosis patients undergoing auto-HCT.

A Patient with Supraclavicular Lymphadenopathy and Anterior Mediastinal Mass Presenting as a Rare Case of Composite Lymphoma: A Case Report and Literature Review.

Composite lymphoma (CL) is a rare disease with 2 distinct lymphomas concurrently arising in a single patient with an estimated incidence of 1-4.7% of newly diagnosed lymphomas per year. CL most commonly involves 2 B-cell non-Hodgkin lymphomas (NHL) or a B-cell NHL with a Hodgkin lymphoma. Our case is unique in that it was a bilineage CL with both a T-cell and B-cell NHL, which has only been reported in a few case reports. A 49-year-old woman presented with several months of progressive cough, weight loss, dyspnea, and supraclavicular lymphadenopathy. Computed tomographic imaging done upon admission to the hospital found that she had extensive anterior and middle mediastinal lymphadenopathy as well as bilateral supraclavicular lymphadenopathy. The patient underwent an excisional biopsy on the supraclavicular lymph node and was found to have a composite lymphoma involving both a T-cell and B-cell NHL. Her final pathological diagnosis was peripheral T-cell lymphoma and lymphoplasmacytic lymphoma. The patient was found to have stage IIIB disease. Her HIV, hepatitis panel, and tuberculosis tests were all negative. She then underwent chemotherapy with dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab). The patient showed a complete response and was then referred to a bone marrow transplant center for an autologous hematopoietic stem cell transplant. CL is a rare disease composed of at least 2 distinct lymphomas concurrently arising in a single patient. Due to the complexity in having to treat multiple types of lymphoma simultaneously CL presents challenges with treatment and assessing prognosis.