Post Autologous Hematopoietic Stem Cell Transplantation Research Articles

Cognitive performance and mortality among patients receiving autologous hematopoietic stem cell transplant

Objectives Patients undergoing autologous hematopoietic stem cell transplant (HCT) are at risk for death and remain understudied relative to those undergoing allogeneic HCT. Cognitive functioning may be a useful indicator of mortality risk. We examined cognition among patients who underwent autologous HCT and its relationship to mortality. Methods Participants (N = 51; 11 patients deceased) completed tasks of processing speed, working memory, executive-mediated learning, and visual recall using the computerized CogState battery prior to HCT, 30 days post-autologous HCT, and 100 days post-autologous HCT. Results Slower processing speed (HR = 3.00) and more errors on an executive-mediated visual learning task (HR = 2.78) prior to HCT were associated with an increased risk of death following HCT. Our sample size limited longitudinal analyses of whether cognitive change predicted survival, however descriptive cognitive data of the deceased versus living patient’s performances over time suggested different patterns of performance across groups. Conclusions Pre-HCT cognition may have utility as an indicator of mortality risk following autologous HCT. More research is needed to examine whether cognitive changes after HCT could also predict mortality.

Long-term outcomes and renal responses following autologous hematopoietic stem cell transplantation for light chain deposition disease: a retrospective study on behalf of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation.

There is little long-term outcome data on the efficacy of autologous hematopoietic stem cell transplantation (ASCT) in light chain deposition disease (LCDD). We identified 51 LCDD patients in the EBMT registry who had undergone upfront ASCT between 1995 and 2021. The median serum creatinine was 280 μmol/L and 45% required renal replacement therapy (RRT) at time of transplant. The melphalan dose was 100mg/m2 in 23%, 140mg/m2 in 55% and 200 mg/m2 in 21%. The rate of very good partial response or better improved from 41% pre-transplant to 66% at Day +100 post-ASCT. In RRT-independent patients, there was a modest improvement in renal function within the first 3 months; the median eGFR increased from 44 to 51 ml/min/1.73 m2. There was no further change between 3 and 12 months post- ASCT. No patient who was RRT-independent at ASCT became RRT dependent by Day + 100 post-ASCT. Median follow-up post-ASCT was 84 months (IQR: 46-122). At 6-years post ASCT, overall survival (OS) was 88% (95% CI: 78-98%) and PFS was 44% (95% CI: 28-60%). The 2-year cumulative incidence of relapse and non-relapse mortality (NRM) was 17% (95% CI: 6-27%) and 2% (95% CI: 0-6%), respectively. The cumulative incidence of renal transplantation at 4 years after ASCT was 27% (95% CI 13-41) with renal transplantation performed between 6.3 and 52.9 months post-ASCT (median 24.7 months). ASCT represents a feasible option for LCDD patients even if RRT dependent at time of transplant. Outcomes are favourable with low NRM and good long-term OS.

Patterns of Change in Multiple Myeloma (MM) Clone Size with Autologous Hematopoietic Stem Cell Transplantation (ASCT) Assessed By Next Generation Sequencing (NGS) in Patients (pts) Receiving Modern Therapy

Background Measurable residual disease (MRD) is a quantitative, dynamic prognostic marker of progression free and overall survival in MM. With modern triplet and quadruplet induction strategies deep responses are the norm and the incremental effect of ASCT impact may vary substantially among pts and be influenced by disease and treatment features. However, the accurate characterization of the impact of ASCT is diluted by measuring a disease surrogate (paraprotein) instead of clone size. We examine the quantitative impact of ASCT on MM clone size by serial NGS testing before and after ASCT and evaluate disease and induction treatment features that modulate this impact. Methods We included pts with newly diagnosed MM from five US centers, who received modern triplet and quadruplet induction followed by single melphalan ASCT between 3/2018 and 5/2023 with MRD testing (ClonoSEQ®) pre and post ASCT. ClonoSEQ® platform utilizes NGS to quantify unique immunoglobulin genes rearrangements associated with MM clone, therefore directly capturing clone size. We excluded pts with clone size <10 -5 prior to ASCT. We explored patient-, disease-, and treatment features influencing clone size reduction with AHCT by 1 log 10. We used binary logistic regression to identify factors associated with ≥1 log 10 clone reduction (60-100 days post ASCT). Results One hundred and forty-nine pts with NDMM had pre and post ASCT results and pre ASCT MRD ≥10 -5 and met the inclusion criteria. The median age was 63 years (35-79), 37 pts (25%) ≥70 years, 62% male, 27% Black, 23% ISS3 and 16% RISS3. Seventy-three pts (49%) had high risk chromosomal abnormalities [HRCA, gain/amp(1q), t(4;14), t(14;16), t(14;20) or del(17p)]); 72 pts (48%) had 0 HRCA, 50 (34%) had 1 HRCA, and 23 (15%) had 2+ HRCA. AntiCD38 monoclonal antibody (mAb) was part of induction in 125 (84%) pts [68 pts quadruplet containing carfilzomib; 53 pts quadruplet containing bortezomib], 28 pts received triplets. Eighty-seven pts (58%) had >1log 10 reduction in MRD burden with ASCT. The median log reduction in MRD burden was 1.15 (IQR 0.65-1.75). For pts with 0, 1 and 2+ HRCA, 47% (34/72), 68% (34/50), 74% (17/23) had a >1 log 10 reduction in clone size and the median reduction was 0.96 log 10 (IQR 0.47-1.66), 1.24 log 10 (IQR 0.89-1.91) and 1.5 log 10 (IQR 0.89-2.20), respectively (Figure). Among pts without HRCA, those with hyperdiploid MM had a trend towards less frequent ≥1 log 10 clone size reduction with ASCT (38% vs. 57%, p=0.18). Overall, we saw reduction ≥1 log 10 in clone size in 61% of pts receiving anti-CD38 mAb in induction (N=125) vs. 46% among those who did not (N=24, p= 0.18). Among pts treated with melphalan 200 mg/m 2 (N=113) compared to those who received 140 mg/m 2 (N=36), ≥1 log 10 reduction in clone size was noted in 61% vs. 50% (p=0.25), respectively. In multivariable analysis that included stage, antiCD38 mAb in induction, use of carfilzomib in induction, HRCA and melphalan dose, the presence of HRCA was the only factor associated with greater than 1 log 10 reduction in MRD burden with ASCT [1 HRCA, OR 2.34 (1.07-5.14); ≥2 HRCA, OR 2.71 (0.91-8.03); p=0.049]. Conclusions The impact of high dose melphalan and AHCT on MM clone size is heterogeneous, of greater magnitude in pts with one or more high-risk chromosome abnormalities, and less pronounced in pts with standard risk disease, particularly hyperdiploid MM. The use of antiCD38 mAb in induction regimens or dose of melphalan does not impact the effect of ASCT on MM clone size, likely owing to the distinct mechanism of action of melphalan. This dataset provides context to explore risk- and response-adapted use of ASCT and use of new cellular and non-cellular immunotherapies as post-induction consolidative strategies.

Inotuzumab Ozogamicin in Lymphoid B Cell Malignancy：a Single Center Analysis in the Real World

Background : Recent developments in immunoconjugate usage has changed the landscape of lymphoid B-cell malignancy therapy. Historically, those who relapse from this condition have a dismal prognosis and limited treatment options. One recent development is the inotuzumab ozogamicin (INO), a humanized anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin, which has the potential to reduce the overall toxicity of intensive regimens for ALL, as well as to show therapeutic effects in lymphoid B-cell malignancy. Aims and Methods: The study included B cell-acute lymphoblastic leukemia (B-ALL) (n=23), B/ myeloid mixed phenotype acute leukemia (MPAL) (n=1) and B-cell lymphoblastic lymphoma (B-LBL) (n=3) adult patients who received INO in our center from June 2022 to June 2023. Intravenous INO was given 1 or more doses at the dose of 0.6mg/m2, its clinical efficacy and adverse reactions were explored. Results: In our center, INO was strategically employed in various therapeutic scenarios: induction (n=2), maintenance/consolidation (n=6), minimal residual disease (MRD) clearance (n=5), and the management of relapsed/refractory lymphoid B-cell malignancies (n=14). Of the 27 patients, 14 were subjected to a combination regimen of INO and chemotherapy for recurrent and refractory lymphoid B-cell malignancy. The composition of these patients comprised of 4 individuals who experienced a relapse post-standard chemotherapy, 1 patient with a relapse post-allogeneic hematopoietic stem cell transplantation (allo-HSCT), 4 patients with a relapse post-autologous hematopoietic stem cell transplantation (auto-HSCT), and the remaining 5 patients were categorized as refractory cases. The median number of doses administered was 2 (1-3). Complete remission (CR) or CR with incomplete hematologic recovery (CRi) was observed in 9 out of 14 patients (64.3%) within a median duration of 30 (16-78)days. Partial response (PR) was noted in 2 of the 14 patients (14.3%), rendering the overall response rate (ORR) to be 78.6%. Negative MRD was observed in 7 out of 14 patients (50.0%). Of the 9 patients who achieved CR/CRi, 4 (44.4%) relapsed again with 2 fatalities. The remaining 2 patients attained negative MRD following a second allo-HSCT or INO retreatment. The two patients who achieved PR proceeded to receive chimeric antigen receptor T cell (CART) treatment, with one of them subsequently undergoing allo-HSCT after achieving CR. For the three non-responders (NR), one patient unfortunately passed away while the other two patients remained alive and were either participating in clinical trials or undergoing allo-HSCT after CART. For MRD clearance, it was successfully achieved in 4 out of 5 patients (80.0%)treated with INO within a median period of 45 (28-52)days. However, 2 patients reverted to MRD positivity and 1 died. The other four patients underwent allo-HSCT with neither mortality nor recurrence observed. Moreover, two patients (100%) were treated with a VICLP induction regimen combined with INO, with MRD negativity observed post-treatment. Regarding the remaining six patients, three patients were treated with INO as consolidation therapy due to high-risk factors or the intention to undergo auto-HSCT. Another 3 B-ALL patients treated with INO as maintenance therapy after auto-HSCT or after the remission of recurrence after transplantation. One patient unfortunately experienced a second recurrence four months following INO maintenance. The remaining five patients achieved and have since sustained negative MRD status, preceding INO treatment. Fortunately, no treatment-related fatalities or treatment discontinuation due to adverse events were observed. Notably, 19 out of 27 patients (70.4%) experienced Grade 3-4 hematological toxicity, while 1 out of 24 patients (4.2%) exhibited Grade 3 alanine aminotransferase (ALT) elevation. Veno-occlusive disease (VOD) was not observed. Furthermore, two patients developed septicemia, one each from Escherichia coli and Klebsiella pneumoniae, respectively. Conclusions: Given the well tolerance and improvement in response rates, InO may be an important treatment option not only for patients with relapsed/refractory lymphoid B-cell malignancy, but also for induction, maintenance and MRD clearance treatment. Key words: inotuzumab ozogamicin, acute lymphoblastic leukemia, hematopoietic stem cell transplantation, CD22

Plinabulin to shorten neutropenia and improve quality of life peri-autologous hematopoietic cell transplant.

8023 Background: Plinabulin is a selective immunomodulating microtubule-binding agent, which prevents chemotherapy induced neutropenia (CIN) via a mechanism of action different from that of G-CSF analogues. It has been studied for CIN and anti-solid tumor activity in phase 3 trials. To decrease the period of myelosuppression and obligate neutropenia after high dose melphalan with autologous hematopoietic stem cell transplantation (AHCT) for patients with multiple myeloma, we studied the addition of plinabulin to standard growth factors. Methods: To achieve the primary objective of reducing the duration of absolute neutropenia post AHCT, 40mg of intravenous plinabulin was given 1-3 hours after stem cell infusion (Day 0) with pegfilgrastim on Day +1 in this pilot trial (NCT05130827). Secondary objectives include the safety, tolerability, and toxicity profile of plinabulin in combination with pegfilgrastim, neutrophil and platelet engraftment rate, disease response, progression free and overall survival, patient reported outcome (PRO) assessment of symptom burden, and plinabulin pharmacokinetic profiling. Exploratory objectives include transfusion requirements, phenotypic characterization of neutrophil population through day 30, and analysis of cytokine levels early post AHCT. Results: Between January 2022 and February 2023, 15 patients with median age of 64 (range 54-74) and 33% female received plinabulin after melphalan 140 (n = 4) or 200mg/m2 (n = 11). Median CD34+ cells/kg infused was 4.12 x 10^6 (range 2.18 – 7.85). Half of the patients had hypertension immediately after the plinabulin infusion, which is a known toxicity and resolved within a few hours. Median WBC on Day 0, 1, and 2 was 7.67(3.6 – 11.5), 5.2 (3.2 – 13.6), and 17.1 (5.1-59.1), respectively. Of the 14 patients who have engrafted to date, median time to ANC > 0.5 x 10^9 cell/L was 11 days (range 9-16) with median days from AHCT to ANC < 0.5 of 5 days (range 5-6). The median number of days of ANC < 0.1 and < 0.5 were 2 (range 1-5) and 5 days (range 4-9), respectively. For the 7 patients who had a fever, the median time to fever was 8 days from AHCT (range 8-12), and all except one were peri-engraftment. Median length of stay was 17 days (range 15-21). Median pRBC and platelet transfusions were 0 (range 0-3) and 3 (range 0-11), respectively. Conclusions: Plinabulin appears well tolerated without additional major toxicities post AHCT and provided a high WBC on Day +2 and decreased rate of neutropenic fever. Plinabulin PK, quality of life data, and PROs will be presented. Adjusting the schedule of plinabulin to later post AHCT pre engraftment may further shorten the duration of neutropenia using this novel mechanism of action. Clinical trial information: NCT05130827 .

Cyclophosphamıde–Etoposıde + G-csf Compared to G-csf alone in Perıpheral Blood Stem Cell Mobılızatıon for Multıple Myeloma

Background: Multiple myeloma (MM) is the leading indication of autologous hematopoietic stem cell transplantation (AHSCT). There are different regimens used for peripheral blood stem cell mobilization in MM. A minimum of 2 × 106 CD34 + cells/kg are needed for engraftment. This study that present a comparison of the mobilization outcomes Cyclophosphamide-Etoposide (Cy-Et) + granulocyte-colony stimulating factor (G-CSF) group and G-CSF alone group. Patients and methods: This study has been performed in a retrospective manner. 110 patients with diagnosed MM who underwent stem cell mobilization at Memorial Sisli Hospital between the years of 2013 and 2018 were evaluated. We retrieved data on patient demographics, disease status at mobilization, treatment characteristics, stem cell mobilization, collection and post AHSCT outcomes. For mobilization, 70 patients received cyclophosphamide 1250 mg/m2 for 2 day, etoposide 100 mg/m2 for 3 day and G-CSF 10 mcg/kg/day from day 4 onwards and 40 patients received G-CSF alone. Results: In 98 of 110 patients (89.1%) first mobilization trial was successful. Four patients in the Cy-Et group (5,7%) and eight patients in the G-CSF alone group (20%) were mobilized three times (p=0.001). The number of CD34 in peripheral blood was significantly higher in Cy-Et group (94±14) than G-CSF alone group (54±7) (p=0.04) on the stem cell mobilization time. Stem cell collection was higher in the Cy-Et group (13.8 × 106 CD34 + cells/kg) compared to the G-CSF alone group (8.8× 106 CD34 + cells/kg) (p =0.001). The median time to neutrophil engraftment was 11 and 13 days in Cy-Et group and G-CSF alone group respectively (p=0.014). The median time to platelet engraftment was 15 and 17 days in Cy-Et group and G-CSF alone group respectively (p=0.006). Median 360 ml stem cells in Cy-Et group and 470 ml stem cells in G-CSF alone group were collected and this difference was statistically significant (P=0.001). Conclusion: In conclusion, this study was demonstrated that Cy-Et + G-CSF mobilization provides a higher peripheral CD 34 count, less apheresis sessions, less volume, more stem cell mobilization, earlier neutrophils and platelet engraftment for patients with MM and eligible for AHSCT. Today, Cy-Et + G-CSF mobilization is a really useful method than G-CSF alone.

Low Non Relapse Mortality and Good Hematological Response after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients with Renal Insufficiency at Transplant: A Prospective Société Francaise De Greffe De Moelle-Thérapie Cellulaire Observational Study

Background: High dose melphalan (HDM) followed by autologous hematopoietic stem cell transplantation (ASCT) is widely used in newly diagnosed multiple myeloma (NDMM) patients as upfront therapy. However, the safety and efficacy of ASCT in patients with renal insufficiency (RI) is controversial, which have led to an inconsistent arbitrary cut-off for creatinine clearance (CrCl) for performing ASCT. Here, we analyzed prospectively the outcomes of NDMM patients with severe RI who underwent ASCT. Methods: We enrolled prospectively, from April 2018 to Sept 2020 in 17 SFGM-TC centers, 50 NDMM patients who had a serum CrCl of <40 mL/min (CKD-EPI) at the time of ASCT. They all received bortezomib-based induction therapy and had achieved at least a partial response before proceeding to ASCT. The recommended dose of melphalan was 140 mg/m2 and it was infused at least 3 x106/kg autologous CD34+ cells. Consolidation/maintenance post-ASCT was according to the physician's choice. The primary endpoint was non-relapse mortality (NRM). Overall survival (OS) and progression free survival (PFS) were estimated with Kaplan-Meier method, and cumulative incidence of relapse (CIR) and NRM were estimated using cumulative incidence function to account for competing events of death without relapse or death unrelated to myeloma. Results: At diagnosis, a renal biopsy was done in 9 (no amyloidosis, 6 cast nephropathy and 3 others). 82% were male. The median medullary plasmocytosis was 42% (11-80), light chain MM was frequent in 28 patients (56%), IgG in 13 (26%), IgA in 8 (16%) and 1 IgD. Seven (16%) had extra medullary disease. The ISS score was I (1), II (7) and III (34) (8 missing). At enrollment at the time of ASCT: median age was 56 years (33-68). Induction chemotherapies had included bortezomib plus IMiDs in 28 (56%) patients, CyBorDex in 17 (34%), bortezomib dex in 4 (8%) and 1 other (2%). Thirty nine patients (80%) had received 4 or less cycles of chemotherapy and 13 (26%) had ≥2 lines of chemotherapy. The pre-transplant disease status was sCR in =3 (6%), CR in =7 (14%), VGPR in =22 (45%), and PR in =17 (35%) of patients (1 not evaluable ( NE)). The number of days of cytapheresis was 2 or less in 93% of cases and the median number of CD34+ cells collected was 5.4 x 106 (1.1-15.1) (3 missing).The HCT-CI score was 0 (4), 1 (8), 2 (11), 3 (11), missing (16) and 97% had a Karnofsky score ≥70%. HDM was 100 mg/m2 in 1, 140 mg/m2 in 44/50 patients and 200 mg/m2 in 5/50 with 6 patients receiving a tandem ASCT. Seventy three percent received consolidation post ASCT (1 missing) and 69% had maintenance therapy (lenalidomide: 53%, thalidomide: 26%, bortezomib: 21%). Toxicity: We observed one death during the first 100 days post-ASCT, secondary to a septic shock on day 42. The median time to neutrophil engraftment (>500/mm3) was 13 days (10-136) and to platelet engraftment (>20 000/mm3) 16 days (8-136). Among patients receiving RBC transfusions (43%) and platelet transfusions (49%), the median number of RBC transfusions was 3 (2-14) and that of platelet transfusions was 2 (1-44). Response: Nine patients (60%) achieved dialysis independence from the time of diagnosis: 15 patients were on dialysis at diagnosis, 6 at the time of ASCT and 4 three months post-ASCT. At 100 days post-ASCT, the hematological response had improved in 62 % of patients, from PR to VGPR (15%), from PR to CR/sCR (15%), from VGPR to CR/sCR (30%) and from CR to sCR (2%). The best response obtained was 4 (9%) PR, 18 (39%) VGPR, 19 (41%) CR and 5 (11%) sCR with one patient relapsing and 3 NE. At 2 years, the NRM was 4% (95% CI: 0%-12%), the OS was 84% (95% CI:74%-95%), the PFS was 70% (95% CI:58%-84%) and the CIR was 30 % (95% CI:17%-43%) (Figure). Conclusions: HDM with ASCT proved to be safe and effective in NDMM patients with RI at transplant. NRM was 4% at 2 years and 62% improved their hematological response. Renal response will be reported. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical Outcomes of CD19 CAR-T-Cell Therapy with Axi-Cel in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) with and without Prior Autologous Stem Cell Transplant

Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common form of aggressive non-Hodgkins lymphoma, accounting for up to 40% of cases. Long term remission is achieved in 50-60% of the patients with rituximab and anthracycline based treatment, but the remaining patients will have either primary refractory or relapsed disease. Prior to the advent of CAR-T-cell therapy, salvage chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) was the standard of care for these cases of relapsed or refractory (r/r) disease. For those who relapse post ASCT, options are limited and outcome was dismal. With the results of recent pivotal studies, CAR-T-cell therapy is now offered in patients who are not ASCT candidates and for those who relapse after ASCT. The phenotype of patients who proceed to CAR-T without ASCT is possibly different than those who are able to achieve a clinical response and then proceed to ASCT. While numerous trials have compared the clinical outcomes of ASCT and CAR-T, few have investigated outcomes of CAR-T in previously transplanted versus transplant naïve patients. Wang et al. demonstrated a potential benefit for sequential ASCT and CAR-T in 14 patients with r/r DLBCL, with a median PFS of 14.82 months. Our study compared the clinical outcomes of previously transplanted and transplant naïve patients with r/r DLBCL who received axi-cel (Yescarta) CD19 CAR-T therapy at our center between 2018-2021. Methods Data was collected on 99 patients who received first axi-cel CAR-T therapy at our center for r/r DLBCL between 2018-2021. Of these patients, 84 were transplant naïve and 15 had received prior ASCT. We examined the rate of relapse/progression after CAR-T. Overall survival (OS) was defined as time from date of CD19 CAR-T therapy to death, censored at last known alive. Progression-free survival (PFS) was defined as time from date of CD19 CAR-T therapy to time of disease recurrence or death from any cause, censored at last known alive. Non-relapsed mortality (NRM) was defined as death without relapse or progression. Results 63 patients (64%) were alive as of end of study date. Median follow-up time was 1.70 years (95% CI: 1.54-2.07) for all patients, 1.63 years (95% CI: 1.50-1.99) for transplant naïve patients, and 2.21 (95% CI: 1.09-not reached) for previously transplanted patients. 90-day disease response to CAR-T (CR, PR, SD and PD) was not different for transplant naïve vs. previously transplanted patients (P=0.444). Median OS was not reached for either transplant naïve or previously transplanted patients, with 2-year OS rates of 60% (95% CI: 50-73%) vs. 66% (95% CI: 43-100%) for previously transplanted patients (P=0.23). Median PFS was 0.51 years for transplant naïve patients and not reached for previously transplanted patients, with 2-year PFS rates of 44% (95% CI: 34-56%) for transplant naïve and 56% (95% CI: 33-92%) for previously transplanted patients (P=0.16). 2-year cumulative incidence of relapse or progression was 43% (95% CI: 33-54%) for transplant naïve and 33% (95% CI: 8-58%) for previously transplanted patients (P=0.43). 2-year NRM was 12% (95% CI: 5-20%) for transplant naïve and 11% (95% CI: 0-33%) for previously transplanted patients (P=0.44). In multivariate analysis, bridging therapy, elevated LDH >600 at the time of lymphodepleting chemo, and grade 3 and 4 CRS were associated with worse OS; platelets <75,000 at the time of lymphodepleting chemo, grade 3 and 4 CRS and elevated LDH >600 were associated with worse PFS. There was no difference in the incidence of high grade CRS and neurotoxicity, ICU transfer rate, cytopenias and length of hospitalization between the 2 groups. Conclusions This study showed no significantly significant differences in the OS, PFS, relapse/progression and NRM of r/r DLBCL patients who received CD19 CAR-T-cell therapy (axi-cel) with or without prior ASCT. Other factors such as bridging therapy, elevated LDH and high grade CRS were associated with worse OS. We conclude that prior ASCT does not appear to adversely affect the outcomes of CAR-T-cell therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

High-dose thiotepa, in conjunction with melphalan, followed by autologous hematopoietic stem cell transplantation in patients with pediatric solid tumors, including brain tumors

Among pediatric malignancies, solid tumors, particularly within the central nervous system (CNS), are common. Thiotepa, a myeloablative, high-dose chemotherapeutic (HDT) treatment administered prior to autologous hematopoietic stem cell transplantation (HSCT), can cross the blood-brain barrier and rapidly penetrate the CNS. We evaluated thiotepa HDT in conjunction with melphalan in Japanese patients with pediatric CNS/non-CNS solid tumors in a multicenter, open-label, non-comparative study. Thiotepa (200 mg/m2/day) was administered intravenously (IV) over 24 h on days −12, −11, −5, and −4 before scheduled HSCT. Melphalan (70 mg/m2/day) was administered IV over 1 h on days −11, −5, and −4. The safety analysis population comprised 41 patients, of whom 16 (39.0%) had solid tumors and 25 (61.0%) had brain tumors. The most frequently reported adverse events were diarrhea (40/41 [97.6%] patients) and febrile neutropenia (34/41 [82.9%]). No unexpected safety events were observed, and no events resulted in death or treatment discontinuation. All patients experienced bone marrow suppression and 39/41 (95.1%) achieved engraftment (neutrophil count ≥500/mm3 for 3 consecutive days after HSCT). The survival rate at day 100 post-autologous HSCT was 100%. These data confirm the safety of IV thiotepa plus melphalan HDT prior to autologous HSCT for patients with pediatric CNS/non-CNS solid tumors. Trial registration: JapicCTI-173654.

HUMORAL IMMUNITY RESPONSES AFTER VACCINATION FOR HEPATITIS B VIRUS IN AUTOGRAFTED PATIENTS: A SINGLE CENTER EXPERIENCE

The effectiveness of vaccinations post hematopoietic stem cell transplantation (HSCT), is a reliable marker for immune system's functionality assessment. In autologous HSCT (AHSCT) setting, the general aspect is that the immune system recovers quite soon and patients (pts) are considered to be immunocompetent in a period of approximately 3-6 months post AHSCT. We evaluated the hepatitis B virus (HBV) vaccination responses in autografted pts who were in remission and off chemotherapy post AHSCT. 27 autografted pts aged 51,6 (22-67) ys, who had antiHbs titers <10 IU/ml before AHSCT and at the time of vaccination, were studied. After a successful engraftment the median absolute lymphocytes count at +3 months was 1740(450-4090)/mm 3 . In 4,3(0,6–8,5) ys post AHSCT, 3 doses of recombinant HBV vaccine were given monthly. The response rates for pts who completed 3 vaccine doses, compared with an internal group of healthy individuals, vaccinated in the same period with the same product. After the 1 st , 2 nd and 3 rd dose the response rates in the study group were 11%, 81% and 88% respectively. No factor statistically significantly influenced the achievement of protective antiHbs titers. The responses were lower as compared to product's efficacy profile (19%, 86% and 100% after the 1 st , 2 nd and 3 rd dose respectively), while in the comparative analysis with the internal control group, a trend for inferior responses in autografted pts was also noticed (88% vs 100%, p=0,07). This study, in a relatively homogenous group of pts, to our knowledge, is the only one that directly compares the HBV vaccine responses in autografted pts with healthy individuals. Although vaccination was offered late post AHSCT, the responses were lower compared to healthy individuals, indicating a possible long lasting immune impairment post AHSCT highlighting the necessity of prolonged surveillance and intensified vaccination programs for autografted pts.

Estimating the Incidence-Based Cost of Illness Due to Hematopoietic Stem Cell Transplantation Using One-Year Insurance Claim Data in Korea.

Long-term follow-up data are required for incidence-based cost-of-illness (COI) studies, and it is difficult to carry out such assessments. To overcome this limitation, we estimated the acute and maintenance-state costs of hematopoietic stem cell transplantation (HSCT) using 1-year claim data. Using Korean National Health Insurance (NHI) data from 2016, 2017, and 2018, we identified patients receiving HSCT based on the procedure code "X5*" (i.e., HSCT). The post-HSCT group was defined as patients without the "X5*" code, but with the code "Z948 (other transplanted conditions)" and indications of HSCT (referring to those who had received HSCT). Mean annual medical use and costs were computed using the monthly values available for each patient. The mean number of hospitalizations/year, outpatient visits per year, hospitalization days/year, and length of stay (LOS)/hospitalization were 8.14, 35.80, 97.16, and 14.72, respectively, for allogeneic HSCT patients (n = 56); 8.08, 33.58, 73.04, and 10.63, respectively, for autologous HSCT patients (n = 89); 2.93, 29.40, 50.95, and 20.84, respectively, for post-allogeneic HSCT patients (n = 40); and 1.72, 16.38, 30.11, and 19.29, respectively, for post-autologous HSCT patients (n = 252). The estimated annual NHI-covered medical costs (US dollars) were $38,833-$40,876 for the allogeneic HSCT group, $1749-$6744 for the post-allogeneic HSCT group, $21,231-$22,863 for the autologous HSCT group, and $3954-$5352 for the post-autologous HSCT group. This study describes an alternative method for conducting incidence-based COI studies using cross-sectional claims data.

Impact of second primary malignancy post-autologous hematopoietic stem cell transplantation on outcomes of multiple myeloma: A CIBMTR analysis.

8057 Background: Following autologous hematopoietic stem cell transplant (auto HCT), maintenance therapies improve survival, reduce relapse risk in multiple myeloma (MM), and are the de facto standard-of-care. However, clinical trials have shown an increased risk of second primary malignancies (SPM) with maintenance therapy, including second hematological malignancies (SHM). We examined data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry to evaluate the impact of SPM on progression-free (PFS) and overall survival (OS) and the utilization of allogeneic HCT in patients with therapy-related myeloid neoplasms (t-MN). Methods: Adult patients (pts) with MM who underwent first auto HCT in the United States with a melphalan conditioning regimen from 2011-2018 and subsequently received maintenance therapy were included (N=3948). The primary endpoint of interest was the impact of SPM and SHM on OS. Multivariate analytic (MVA) modelling was applied, accounting for competing risks while integrating significant covariates to determine the impact of SPM on PFS and OS. Finally, we studied the utilization and survival following allogeneic HCT for SHM. Results: Baseline characteristics were similar between the two groups. Maintenance regimens used were lenalidomide (2836, 72%), bortezomib (370,9 %) or lenalidomide + bortezomib (372, 9%) based combinations. At a median follow up of 37 months, 175 (5%) pts developed SPM, including 112 (64%) solid 36 (21%) myeloid, and 27 (15%) lymphoid cancers. In MVA, the development of SPM and SHM was associated with an inferior PFS (HR 2.62, P&lt;0.001 and HR 5.01, P&lt;0.001, respectively) and OS (HR 3.85, P&lt;0.001 and 8.13, P&lt;0.001, respectively). The two commonest causes of death were MM (42%) and SPM (30%) for those developing SPM. Similarly, MM (53%) and SHM (18%) were the two commonest causes of death for those developing SHM. Nine (14%,5 t-MDS and 4 t-AML) of 63 patients with SHM underwent an allogeneic HCT. Patients undergoing allogeneic HCT were more likely to have Karnofsky score ≥90 (100% vs. 50%, P=0.02) compared to those who did not. One year survival from allo SCT was 66.7% (CI 34.6-92%). Conclusions: The three-year cumulative incidence of SPM was 3.3 (2.6-4)% in this large contemporaneous CIBMTR cohort. Disease relapse remains the primary cause of death in MM patients who develop SPM or SHM. Given the median OS for MM is now &gt; 10 years, longer follow-up is needed to assess the SPM and SHM risks with maintenance therapy post-auto HCT.

Early infection in post-autologous hematopoietic stem cell transplant patients: Princess Noorah Oncology Center experience.

Objectives:To assess local epidemiology and risk factors for bacterial, fungal, and viral infections among the autologous bone marrow transplant population.Methods:This study is a retrospective correlational cohort design comprising 150 adult patients who underwent autologous transplants at Princess Noorah Oncology Center, Jeddah, Saudi Arabia between 2014 and 2020.Results:The study findings indicate that bacterial infection prevalence differed significantly across the different disease status pre-salvage as patients with the relapsed disease were more likely to have bacterial infections. The median of engraftment days differed significantly between those who had a bacterial infection and those who did not. Interestingly, previous pneumonia infection had a positive relationship with the number of hospital stays.Conclusions:Bacterial infections are the dominant type of infection among the autologous patient population. The research reflects authentic practice and reports unique characteristics of autologous transplant patients in terms of the prevalence and types of infection these patients experience.

Post Autologous Stem Cell Transplant Light Chain Response Is a Prognostic Marker in Multiple Myeloma Patients in PR/ VGPR after Induction Therapy

BackgroundMultiple myeloma (MM) is a monoclonal B-cell malignancy with a terminally differentiated plasma cell phenotype and monoclonal immunoglobulin production and subsequent end organ damage. Current treatment paradigm includes autologous hematopoietic stem cell transplant (ASCT) after initial induction with combination doublet/ triplet therapy. While complete response (CR) is ideal as it correlates to improved OS, many patients undergo ASCT in VGPR or PR. Previous studies have suggested that rapid reduction in serum free light chains in response to chemotherapy may be representative of a poorly differentiated clone and hence may carry a worse prognosis. We evaluated free serum light chain response of pts with MM in VGPR or PR after ASCT to determine its impact on post ASCT outcomes.MethodsAfter obtaining Wayne state university institutional review board approval, we retrospectively studied pts with MM in PR or VGPR who underwent first ASCT at out institution between Jan, 2002 to Jan, 2012. Data was collected on baseline demographics, ISS stage at diagnosis, cytogenetics at diagnosis, light chain and M spike at diagnosis, date of transplant, melphalan dose, light chain and M protein at diagnosis, just prior to transplant (0), 3, 6 and 12 month after ASCT and post transplant maintenance lenolidomide use. Responses after induction were assessed using IMWG response criteria. Post ASCT, pts were grouped based on the light chain responses (‘Up’ if relative change ≥25% increase, ‘Down’ if >25% decrease, and others as “stable”). We also assessed response with M protein using same criteria. OS was calculated as the time from the date of transplantation to death from any cause. Patients, who were alive, were considered censored at the date of last observation. PFS was calculated as the time from the date of transplantation to the date of progression (based on IMWG criteria or need for restarting therapy) or death from any cause. Univariable and multivariable Cox proportional hazards regression models were fit to assess associations between six prior chosen predictors (age, dose of melphalan, stage, disease status, post-transplant len, and light chain response postASCT) and survival benefit (PFS and OS).ResultsWe identified 231 pts who underwent AutoSCT; 193 pts (84%) had follow up data for 1 yr and were included. There were 104 (54%) male pts and 145 (75%) were Caucasian. 95% had one line of therapy prior to ASCT and 102 (53%) were in VGPR. Median time to transplant was 7.54 months .Post ASCT 38 pts had stable response by light chain criteria(21 VGPR, 17 PR), 58 pts up (42 VGPR, 28 PR) and 97 down (39 VGPR and 91 PR. M protein values were available for 153 pts and consensus analysis of the 3 clusters with both light chain and M peak values significantly concordant (p = 0.003) Forty percent of all pts received post-transplant len maintenance. PFS in the ‘stable’ and ‘down’ gps were similar (HR 1.31, 95%CI 0.78-2.21 p=0.31). OS was significantly improved in ‘stable’ vs ‘down’ gp (HR2.77 (95% CI 1.26-6.11; p=0.01). On multivariate analysis, post-transplant len was associated with increased PFS (HR 1.57; 95CI 1.05-2.34 p=0.03) and OS (HR 1.96; 95 CI 1.14-3.36, p=0.01)ConclusionASCT following induction chemotherapy is currently the standard therapy for eligible MM pts. While response to induction therapy has been prognostic, impact of continued response post ASCT is unclear. We demonstrate that light chain response post AutoSCT correlates with M protein and can be used as a marker to assess response post-ASCT. In our cohort, patients with stable serum light chains / M-spike post ASCT had at least equivalent outcomes to patients who had further decrease in their serum markers. Post ASCT len maintenance was found to be associated with improved PFS and OS. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effect of Dosing Bortezomib According to Adjusted Body Surface Area in Multiple Myeloma

Introduction:Multiple myeloma (MM) is the second most common hematologic malignancy in the U.S., accounting for 15% of hematologic malignancies. MM five-year survival rates have improved from 25.8% in 1980 to their current rate of 49.6% (SEER Stat Fact Sheets: Myeloma). Grade 2 or higher peripheral neuropathy (PN) has been reportedin up to 39% of patients on bortezomib, with 31% of patients requiring a dose reduction and 9% requiring discontinuation (Velcade [bortezomib] injection prescribing information; Blood 2008 112:1593-99). Although dosing recommendations are available to help limit PN in patients at high risk of developingPN, there is limited evidenceon how these dose adjustments relate toobese patients receiving bortezomib therapy. The American Society of Clinical Oncology (ASCO) guidelines recommend avoiding unnecessary dose reductions in obese patients, especially when the goal of treatment is cure (J Clin Oncol 30: 1553-61). To date, no studies have evaluated dosing bortezomib according to an adjusted body surface area (BSA) in MM, a difficult-to-cure disease, mainly affecting older people with other co-morbidities.Objectives:To evaluate the effect of an adjusted bortezomib dosing scheme utilized at the University of Iowa in MM patients post-autologous hematopoietic stem cell transplant (HSCT). The primary objectivewas the incidence of neuropathy requiring MM therapy dosage adjustment or discontinuation including the following: adjustment in bortezomib therapy due to neuropathy, adjustment in any MM regimen due to neuropathy, discontinuation of thalidomide, and discontinuation of thalidomide due to neuropathy. Secondary objectives included the percentage of patients with disease progression while on bortezomib therapy and percentage of patients deceased due to MM at data collection.Methods:This is a single-center, retrospective chart review of MM patients with a BSA >2.0 and/or weight >60 kg treated with bortezomib post-autologous HSCT between 01/01/14 and 01/31/16. Two dosing schemes were evaluated, a dose-adjusted and a non-adjusted version (referred to as protocol vs. non-protocol dosing, respectively). Protocol dosing was defined as bortezomib 1 mg/m2 intravenously on days 1, 4, 15 and 18 q 4 weeks with a maximum dose of 2 mg or BSA capped at 2.0 m2 while using an adjusted body weight when weight is >60 kg. Patients that received non-protocol dosing received bortezomib 1 mg/m2 intravenously. Statistical analysis of baseline characteristics was performed using Fisher's exact test for nominal data and T-test for continuous data. Primary and secondary objectives were evaluated using a multiple regression analysis.Results:71 patients were identified, of which 33 received non-protocol dosing, 31 received protocol dosing, and 7 were excluded due to the inability to verify outside infusion center dosing. Baseline characteristics between the non-protocol and protocol dosing group were well matched and no statistically significant difference was seen in age at bortezomib initiation, mean BSA, gender, current enrollment in a HCCC clinical trial, time of bortezomib therapy, or HSCT history. No statistically significant difference was seen between patients receiving non-protocol versus protocol dosing in primary or secondary study objectives, including the following outcomes: change in bortezomib therapy due to neuropathy (18.2% vs. 12.9%, p>0.05), change in regimen due to neuropathy (33.3% vs. 32.3%, p>0.05), discontinuation of thalidomide (36.4% vs. 35.5%, p>0.05), discontinuation of thalidomide due to neuropathy (21.2% vs. 22.6%, p>0.05), disease progression while on bortezomib (12.1% vs. 6.5%, p>0.05), deceased due to MM at data collection and disease progression while on bortezomib therapy or death at data collection (21.2% vs. 16.1%, p>0.05).Conclusion:The use of a weight adjusted dosing protocol for bortezomib in obese patients did not appear to decrease the incidence of neuropathy, specifically neuropathy leading to alterations in MM therapy. Although this was a relatively small study and further evaluation would be beneficial, the percentage of patients with disease progression or death while on bortezomib therapy was not found to be affected by the weight adjusted protocol. These results are in line with the 2012 ASCO statement that recommends avoiding unnecessary dose reductions while treating obese patients with cancer. DisclosuresNo relevant conflicts of interest to declare.

Update of a phase II, multicenter study of high-dose chemotherapy with autologous stem cell transplant followed by maintenance romidepsin for T-cell lymphoma.

7533 Background: Peripheral T-cell lymphomas (PTCL) have suboptimal outcomes with conventional chemotherapy. Autologous hematopoietic stem cell transplant (AHCT) is a therapeutic strategy for patients in first complete or partial remission (CR1 or PR1), with median progression-free survival (PFS) after AHCT of 36-48% by intent to treat (d’Amore et al JCO 2012, Reimer et al JCO 2009). Romidepsin (romi) is a histone deacetylase inhibitor approved for treatment of relapsed/refractory T-cell lymphoma. We present updated data of the first multicenter study to evaluate PFS of patients (pts) receiving maintenance therapy with romi after AHCT. Methods: This was a phase 2, open-label, investigator-initiated study (expected PFS 45%, desired PFS 70%; success achieved if 15 or more pts out of 25 were progression-free at 2 years post-AHCT). 26 pts transplanted in CR1 or PR1 were evaluable for the primary endpoint of 2-year PFS (Cohort 1, Table). An exploratory cohort (Cohort 2, n=7) enrolled pts either transplanted ≥ CR/PR2 (n=5) or with high risk histologies (n=2). Pts underwent AHCT with carmustine, etoposide, cytarabine and melphalan (BEAM) conditioning. Maintenance romi 14 mg/m2 started days 42-80 post AHCT; every other week through 6 mon, every 3 weeks through 1 year and every 4 weeks through 2 years post AHCT. PFS was estimated by Kaplan-Meier. Results: 47 pts consented; 13 did not receive romi (no AHCT, n=2; relapse before romi, n=3; cardiac comorbidity, n=3, patient declined, n=5). 1 consented pt did not have PTCL. 15 out of the first 25 pts in Cohort 1 were progression free after 2 years; median follow up of 31 mon (21 - 36 mon). Estimated 2-year PFS was 62% (45-83%, 95% CI); median PFS 30 mon (12.0- NA, 95% CI). In Cohort 2, estimated 2-year PFS was 43% (18 – 100, 95% CI); median follow up of 30 mon (range, 24 – 37 mon); median PFS 14 mon (5 – NA, 95% CI). Across cohorts, 5 pts required dose reduction. The most common toxicities (≥10% of pts, all grades) were fatigue (n=24, 73%), decreased platelets (n=16, 48%) and anemia (n=16, 48%). Conclusions: While the study did not meet its desired primary efficacy endpoint, maintenance romi was well-tolerated with an estimated 2-year PFS of 62%, greater than historical data. A larger, randomized study would be needed to determine the superiority of this approach. Clinical trial information: NCT01908777. [Table: see text]

A Retrospective Comparison of Mitoxantrone-Melphalan and BEAM Conditioning Regimens Before Autologous Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Lymphoma Patients.

High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) is considered the standard therapy for patients with relapsed lymphoma. The aim of our study is the comparison of mitoxantrone-melphalan and BEAM (carmustine, etoposide, cytarabin and melphalan) conditioning regimens before autologous hematopoietic stem cell transplant in patients with lymphoma. This study has been performed in a retrospective manner. Hundred and two patients with relapsed/refractory Hodgkin lymphoma (n = 35) and non-Hodgkin lymphoma (n = 67) who underwent high-dose treatment followed by AHSCT at Memorial Sisli Hospital between 2013 and 2018 were evaluated. We retrieved data on patient demographics, disease status and post AHSCT outcomes. For conditioning regimen 52 patients received mitoxantrone (60mg/m2 × 1day) and melphalan (180mg/m2 × 1day) and 50 patients received BEAM (carmustine at 300mg/m2 × 1day, etoposide at 200mg/m2 × 4days, cytarabine at 2 × 200mg/m2 × 4days and melphalan at 140mg/m2 × 1day). The median age was 45 (18-73) years at the time of the diagnosis. No significant difference was observed in baseline characteristics between groups, including the disease control and previous therapies. Prior to high-dose chemotherapy, 79.4% of the patients were in complete remission (CR) and 20.6% was in partial remission (PR). With a median follow up of 30.5months (range: 1-70months) for the whole cohort, even though the OS was similar in both groups (86% ± 2.4 vs. 84% ± 3.2; p = 0.85), the PFS was noted to be superior among those who received conditioning with BEAM protocol (55% ± 3.7) compared to those with mitoxantrone-melphalan (30.6% ± 2.8; p = 0.006). In conclusion, we demonstrated that the BEAM regimen is an effective high-dose chemotherapy for lymphoma patients before AHSCT. Nevertheless mitoxantrone-melphalan regimen is also an alternative to the BEAM regimen.

Acceptable Toxicity and Good Hematological and Renal Responses after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients with Renal Insufficiency at Transplant: A Prospective SFGM-TC Observational Study

Background: High dose melphalan (HDM) followed by autologous hematopoietic stem cell transplantation (ASCT) is widely used in multiple myeloma (MM) patients as upfront and salvage therapy. However, the safety and efficacy of ASCT in patients with renal insufficiency (RI) is controversial, which have led to an inconsistent arbitrary cut-off for creatinine clearance (CrCl) for performing ASCT. Here we analyzed prospectively the outcomes of MM patients with severe RI who underwent ASCT. Methods: We enrolled prospectively 50 newly diagnosed MM patients who had a serum CrCl of &amp;lt;40 mL/min at the time of ASCT and an age of up to 65 years. They all received bortezomib-based induction therapy and had achieved at least a partial response before proceeding to ASCT. The recommended dose of melphalan was 140 mg/m2 and it was advised to infuse at least 3 x106/kg autologous CD34+ cells. Consolidation/maintenance post-ASCT was according to the physician's choice. The primary endpoint was transplant related mortality. Results: The patients characteristics at enrollment are given in Table 1. We focused on 44 patients who were beyond 3 months post-ASCT. Light chain MM was frequent (12%), 10% had high risk cytogenetics, 36% increased serum LDH and 10% extramedullary disease. Induction chemotherapies included bortezomib plus IMiDs in 25/44 patients with ≥2 lines of chemotherapy in 12/44. The pre-transplant disease status was sCR in =5%, CR in =15%, VGPR in =39%, and PR in =41% of patients. The number of days of cytapheresis was 2 or less in 95% of cases and the median number of CD34+ cells collected was 3.3 x 106 (1.3-9.5). The median time from diagnosis to ASCT was 175 days (103-307). HDM was 140 mg/m2 in 42/44 patients and 200 mg/m2 in 2/44. All, except two, received consolidation post ASCT (34% missing) and 52% had maintenance therapy (all lenalidomide except two receiving bortezomib) and 7% had no maintenance (41% pending). Toxicity: We observed one death during the first 100 days post-ASCT, secondary to a septic shock on day 42. The median time to neutrophil engraftment was 12 days (9-68) and to platelet engraftment 13 days (10-70). Among patients receiving RBC transfusions (75%) and platelet transfusions (84%), the median number of RBC transfusions was 3 (1-6) and that of platelet transfusions was 3 (1-10). Response: Nine patients (70%) achieved dialysis independence from the time of diagnosis: 13 patients were on dialysis at diagnosis, 5 at the time of ASCT and 4 three months post-ASCT. Renal function improved post-ASCT in 34% of patients, 14% moving from a CrCl of &amp;lt;40 mL/min to 60 mL/min and 20% to above 60 mL/min. No patient experienced worsened renal function following ASCT. At 100 days post-ASCT, the hematological response had improved in 49% of patients, from PR to VGPR (18%), from PR to CR/sCR (11%) and from VGPR to CR/sCR (20%). The best response obtained was 5% PR, 34% VGPR, 47% CR and 11% sCR with one patient relapsing. Conclusions: In this preliminary analysis, HDM with ASCT proved to be safe and effective in MM patients with RI at transplant. We observed one death among 44 patients within the first 3 months post-ASCT. A more detailed report of the toxicity will be presented during the meeting along with the survival. Disclosures Vincent: takeda: Membership on an entity's Board of Directors or advisory committees, Other: Congress support; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Congress support; janssen: Membership on an entity's Board of Directors or advisory committees, Other: Congress support. Mohty:Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Stemline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Karlin:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Personal fees; Sanofi: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees. Morel:Janssen: Honoraria. Rubio:Medac: Consultancy; Gilead: Honoraria; MSD: Honoraria; Novartis: Honoraria; Neovii: Research Funding.

A Phase II, Multicenter Study of High Dose Chemotherapy with Autologous Stem Cell Transplant Followed By Maintenance Therapy with Romidepsin for T-Cell Lymphoma

A Phase II, Multicenter Study of High Dose Chemotherapy with Autologous Stem Cell Transplant Followed By Maintenance Therapy with Romidepsin for T-Cell Lymphoma

2694. Incidence of Pneumocytis jiroveci (PJP) Infection with 3-Month Prophylaxis of Aerosolized Pentamidine (AP) in Autologous Hematopoietic Stem Cell Transplantation (HSCT)

BackgroundHSCT patients are at an increased risk of developing PJP after transplant due to treatment induced immunosuppression. Given the risk of cytopenias with co-trimoxazole, AP is utilized as an alternative for PJP prophylaxis. A prior study revealed a 0% (0/19 patients) incidence when AP prophylaxis was given for one year post autologous HSCT. Current guidelines recommend a duration of 3 – 6 months for PJP prophylaxis in autologous HSCT. The primary endpoint of this study was to assess the incidence of PJP infection within one year post autologous HSCT in patients who received 3 months of AP. Secondary endpoint was a cost comparison of 3 months compared with 6 months of AP.MethodsA single-center, retrospective study of adult autologous HSCT patients at Yale New Haven Hospital between February 2013 and December 2017 was performed. Patients were excluded if: <18 years of age, received < or >3 months of AP, changed to alternative PJP prophylactic agent or received no PJP prophylaxis, received tandem HSCT, deceased prior to one year post-transplant from a non PJP-related infection, HIV positive, or lost to follow-up. Pentamidine was given as a 300 mg inhalation monthly for 3 months starting Day +15 after autologous HSCT.ResultsA total of 288 patients were analyzed, no PJP infections occurred within one year post HSCT. Additionally, 187 (65%) patients received treatment post HSCT with 135/215 (63%) receiving maintenance immunomodulatory drugs for myeloma and 40/288 (14%) patients developing relapsed disease. 43% of the chemotherapy regimens for relapsed disease included high dose corticosteroids. The cost difference of using 3 months vs. 6 months of AP is $790, reflecting the cost of drug and its administration. Applying our incidence of 0%, potential cost savings of 3 months vs. 6 months of AP would be $330,000 over 5 years or $66,000 per year.ConclusionThree months of AP for PJP prophylaxis in autologous HSCT patients is safe and effective as well as cost-effective compared with a 6 month regimen.Disclosures All authors: No reported disclosures.