Hematopoietic Stem Cell Transplantation Group Research Articles

Clinical Feature and Effect of Demethylation Therapy in Pediatric Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes

Objective:To better understanding of the clinical and biological features of childhood AML-MRC, in this study we retrospectively investigated 70 children with AML-MRC admitted to our hospital and compared with AML-NOS. We also analyzed the effect of demethylation drugs in introduction therapy among these patients. Study design: This retrospective cohort study was conducted at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (IHCAMS). Newly diagnosed AML patients at our hospital between January 2009 and December 2021 with complete data regarding baseline characteristics and treatment outcomes were reevaluated as having AML-NOS or AML-MRC according to the 2016 WHO classification of myeloid neoplasms and acute leukemia, strictly excluding cases of therapy-related myeloid neoplasms and AML with recurrent genetic abnormalities. Patients with acute megakaryocytic leukemia were also excluded. Clinical and laboratory data were searched in electronic medical records. Follow-up information was obtained from electronic records or by contacting family members and was initialized from the day of diagnosis to May 31, 2022, or the day of death. Results: Among the 779 newly diagnosed AML patients in our center, 70 patients met the diagnostic criteria of AML-MRC and 73 patients were AML-NOS. Patients with AML-MRC had lower white blood cell count (9.1 (IQR 3.0~30.0) ×109/L vs.17.6 (IQR 5.9~86.8) ×109/L, p=0.002), lower hemoglobin level (74.5 (IQR 63.5~ 86.0) g/L vs. 80.0 (71.0, 94.0) g/L, p=0.025) and lower bone marrow proliferation level (p=0.001) compared with patients with AML-NOS. More FLT3-ITD positive patients were found in AML-NOS patients than AML-MRC patients (33.8% vs. 7.1%, p<0.001). Among the 70 AML-MRC patients, 41(58.6%) were diagnosed by myelodysplasia-related cytogenetics, 10(14.2%) from MDS history, and 19 (27.1%) from a multilineage dysplasia. Monosomy 7 or deletion 7q(-7/7q-) is the most frequent cytogenetic abnormality (21.6%) followed by complex karyotype (18.8%) in AML-MRC patients. Totally 56 AML-MRC patients and 71 AML-NOS patients accepted chemotherapy in out center. Induction treatment for 69 AML-NOS patients were idarubicin/ cytarabine/ etoposide (IAE) or mitoxantrone/cytarabine/ etoposide (MAE) therapy. For AML-MRC patients, demethylation drugs alone or demethylation drugs combined above regime were also used (15 case) besides IAE/MEA therapy (35 case). Six AML-MRC patients and 2 AML-NOS patients accepted homoharringtonine/cytarabine/ granulocyte colony-stimulating factor (HAG) and 3 patients received hematopoietic stem cell transplantation (HSCT) without induction chemotherapy. Overall complete remission (CR) rate of 1 course were 51.0% in AML-MRC and 68.2% in AML-NOS patients. In IAE/MAE group, higher CR rate were seen in AML-NOS patients (70.3%) than AML-MRC patients (48.4%) p= 0.06). AML-MRC patients treated with demethylation drugs seemed to have higher CR rate than introduced by IAE/MAE (64.2 % vs. 48.3%, p= 0.39). HSCT in CR1 were conducted in 29 AML-MRC patients and 19 AML-NOS patients. Median follow-up periods were 2.17 in AML-MRC group and 2.43 years in AML-NOS. Three-year overall survival (OS) and event-free survival (EFS) were 54.4% (95%CI 42.4%~69.8%) and 75.7% (95%CI 62.8%~91.1%) for AML-MRC, 42.3% (95%CI 30.2%~59.2%) and 45.8% (95%CI 32.8%~63.9%) for AML-NOS patients. Cox analysis revealed that HSCT were associated with higher OS (HR 0.21,95%CI 0.1~0.41, p< 0.001). In AML-MRC patients, 3-year OS in HSCT group were significantly higher than that in non-HSCT group [83.4% (95%CI,69.6%~99.8%) vs. 28.0% (95%CI,14.6%~53.9%), p<0.001]. AML-MRC patients with myelodysplasia-related cytogenetics exhibited lower 3-year OS (41.9% ,95%CI,27.5%~63.8%) compared with MDS history group (64.8% (95%CI,39.3%~100.0%) and multilineage dysplasia (77.1% (95%CI,57.3%~100.0%). complex karyotype (41.9% ,95%CI,27.5%~63.8%) and -7(7q-) (40.0% ,95%CI,21.5%~74.3%) AML-MRC patients had lower 3-year OS than normal karyotype (42.3%, 95%CI,21.8%~82.0%) and the other abnormal karyotype (63.5% ,95%CI,37.3%~100.0%) but without statistical difference. Conclusions: Childhood AML-MRC exhibited a comparable adverse outcome with AML-NOS which can be significantly improved by HSCT therapy. Demethylation may help improve the CR rate of AML-MRC. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Hypofibrinolysis in Pediatric Patients with Veno-Occlusive Disease in Hematopoietic Stem Cell Transplantation

Background Veno-occlusive disease (VOD) is a serious complication of hematopoietic stem cell transplantation (HSCT) with a high incidence in pediatric patients (11-27%). In clinical practice, VOD is diagnosed with criteria including weight gain, ascites, hepatomegaly, hyperbilirubinemia, and refractory thrombocytopenia. To date, there are no established markers for an earlier diagnosis of VOD. The aspect of assessing hypofibrinolysis, which plays a role in VOD pathogenesis, has not been elucidated. This study aimed to detect signs of hypofibrinolysis in HSCT and VOD patients using thrombelastography parameters and to discover correlations between alterations of these parameters and established symptoms of VOD. Patients and Methods Patients admitted for HSCT to the pediatric HSCT ward at the University Children's Hospital Tübingen, Germany, between May 2020 and November 2021 were prospectively enrolled (study group). Patients who underwent minor surgical procedures or follow-up blood tests years after recovering from oncological diseases and who were otherwise healthy, were recruited as a control group. Blood samples for thrombelastography (EX and TPA test, including the coagulation time (CT), clot formation time (CFT), clot amplitude after 5 minutes (A05), maximum clot firmness (MCF), maximum lysis (ML), α-angle, and lysis time (LT)) were taken once to twice weekly in addition to daily routine blood tests in patients undergoing HSCT. Routine testing included blood counts, coagulation parameters, d-dimers, and bilirubin. VOD symptoms were monitored daily and body weight was measured twice a day. Ultrasound screenings for ascites, progredient hepatomegaly, and portal venous flow velocity were performed in case of suspected VOD. All patients received intravenous anticoagulation with 100 IU/kg and day of unfractionated heparin. Of the control group patients, 6 ml blood was collected once per patient for routine coagulation testing and thrombelastography. Results A total of 51 patients with a median age of 7.8 years were recruited in the study group. Of these patients, five (9.8%) developed VOD and received defibrotide treatment. The VOD was graded moderate (n=2; 4%), severe (n=1; 2%) or very severe (n=2; 4%). Defibrotide treatment was initiated for 4 weeks or until the resolution of symptoms in standard dosing (25 milligrams per kilogram per day (mg/kg/d)) in four doses over 2 hours). The control group consisted of 55 patients with a median age of 6.7 years. A significant difference in thrombelastographic measurements was observed when comparing the VOD to the HSCT group. The lysis time after activation of fibrinolysis in the TPA test was prolonged in the VOD group at 3 weeks after HSCT (d+14 to +21: VOD: 330±67 seconds, HSCT: 246±53 seconds, p=0.0106). Additionally, a significant difference between the VOD and control groups was observed in days +14 to +21 (control: LT 234±50 seconds, p=0.0299). For the time points of day 0 to +6 and day +7 and +13 after HSCT lysis time was also prolonged in VOD patients, but without statistical significance (LT: d0 to +6: VOD: 304±57 seconds; HSCT: 251±67 seconds, p=0.06; d+7 to +13: VOD: 278±34 seconds; HSCT: 255±70 seconds, p=0.12). It was observed that LT correlated positively with weight gain (>5%), progredient hepatomegaly, right upper quadrant pain and reduced portal venous flow velocity (d0 to d+6: weight gain: r=0.31, p=0.0351; pain: r=0.44, p=0.0018; hepatomegaly: r=0.37, p=0.0108; d+7 to +13: pain: r=0.35, p=0.0143; hepatomegaly: r=0.39, p=0.0058; d+14 to d+21: weight gain: r=0.42, p=0.0035; pain: r=0.37, p=0.0103; hepatomegaly: r=0.44, p=0.0020; reduced portal venous flow velocity: r=0.35, p= 0.0167). Conclusions The results suggest that HSCT patients and patients diagnosed with VOD show signs of hypofibrinolysis. Fibrinolysis can be assessed in a rapid and accessible way via thrombelastography. Therefore, thrombelastography might be a useful tool to facilitate early diagnosis of VOD and to identify high-risk patients. Larger studies are needed to determine specific cut-off-values. Stefanie Hammer and Michaela Döring contributed equally to this work.

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.

Treatment for relapsed acute promyelocytic leukemia: what is the best post-remission treatment?

BackgroundArsenic trioxide (ATO) is the standard treatment for relapsed acute promyelocytic leukemia (APL). However, consensus on post-remission therapies is still lacking.MethodsWe evaluated 52 patients who experienced relapse following initial treatment of APL between 2000 and 2019 at Catholic Hematology Hospital. Among them, 41 patients received reinduction treatment, 30 with ATO-based regimen, whereas 11 with conventional intensive chemotherapy (IC).ResultsThe ATO reinduction group showed a significantly higher second molecular complete remission (mCR2) rate, superior neutrophil and platelet recovery, and a lower infection rate than the IC reinduction group. No significant differences were observed in survival outcomes after post-remission treatment among the ATO-based (N=19), autologous (N=12), and allogeneic (N=6) hematopoietic stem cell transplantation (HSCT) groups. In the ATO-based and autologous HSCT groups, among patients with mCR2 after ATO reinduction, nine and five patients experienced a second relapse, respectively (50.7% vs. 41.7%, P=0.878). Among these patients, seven received salvage allogeneic HSCT; six remained alive. The other seven patients received ATO without HSCT. Five died from disease progression, and two survived and have been in mCR2 since.ConclusionPost-remission treatment outcomes of patients with relapsed APL were not significantly different, regardless of the treatment option, suggesting the feasibility of ATO-based treatment without HSCT in mCR2. Allogeneic HSCT may be an effective salvage treatment modality for patients with a second relapse. Owing to a few cases of relapsed APL, multicenter prospective studies may help elucidate the efficacy of each post-remission treatment.

O-267 Uterine volume is dramatically decreased in Stem Cell Hematopoietic Transplantation childhood survivors whatever the conditioning regimen. A case-control MRI study in the L.E.A cohort

Abstract Study question What is the impact of the type of myeloablative conditioning (MAC) regimen applied for hematopoietic stem cell transplantation (HSCT) on uterine volume of childhood leukemia survivors? Summary answer Uterine volume is significantly decreased after HSCT. Not only Total Body Irradiation (TBI), but also high-dose chemotherapy-based regimens containing alkylating agents induce uterine damage. What is known already Premature ovarian failure after HSCT is well known, as well as the uterine damage induced by TBI on uterine volume. A few studies have reported smaller uterus after HSCT in women treated with chemotherapy only. In these studies, uterus volume was assessed by a transabdominal and/or transvaginal ultrasonography, and primary diagnosis, age at treatment and chemotherapy regimen were heterogeneous. These preliminary results suggested that alkylating agents could induce uterine damage, as well as they induce fibrosis and vascular damage in ovarian stroma. The impact of chemotherapy on myometrium and uterus is still few investigated. Study design, size, duration A prospective multicentric national study was conducted between 2017, November and 2021, June in 16 University Teaching Hospitals that are following more than 4 500 childhood acute leukemia survivors enrolled in the L.E.A cohort. We included 88 adult women treated for a childhood acute leukemia with HSCT and who agreed a pelvic MRI assessment. Every case was matched 1:1 to control women who underwent MRI for benign ovarian cysts or benign pelvic pathology. Participants/materials, setting, methods Pelvic MRI scans were performed with a 1.5-T or 3T magnetic resonance scanner, including diffusion-weighted imaging sequences. Scans were centralized for a double-blinded lecture by two radiologists. The main outcome was the uterine volume. The secondary outcomes were uterine body-to-cervix ratio and apparent diffusion coefficient (ADC). Univariate and multivariate analyses have investigated the association of clinical and imaging variables with conditioning regimen and age at HSCT. Main results and the role of chance The mean age in HSCT group was 26.5 + 6.3 years. Mean age at HSCT was 9.1 + 0.3 years with a mean follow-up of 16.4 + 0.5 years. Among the 88 women included in HSCT group, two groups of conditioning regimens have been compared to the control group: a chemotherapy-only MAC regimen group with high dose of alkylating agents (n = 34) and one TBI-based regimen group (n = 52). Two MRI scans were not available. Among HSCT group, 75 women were considered as “normally impregnated” by estrogens, by hormone replacement therapy (HRT) for premature ovarian insufficiency (POI) or thanks to a residual ovarian function. Uterine volume was significantly decreased both after chemotherapy-only MAC regimen and after TBI, with respectively 45.3 + 5.6 and 19.6 + 1.9 mL Vs 79.7 + 3.3 mL in control population (p &amp;lt; 0.01). In chemotherapy-only MAC regimen group, uterine volume was dramatically decreased in POI women without HRT compared to those having a hormonal impregnation (15.2 + 2.6 Vs 49.3 + 6 mL, p &amp;lt; 0.05). In contrast, after TBI, uterine volume was similar in all women, with no positive effect of HRT on uterine volume (respectively 16.3 + 2.6 Vs 20.1 + 2.2 mL). Limitations, reasons for caution The number of pregnancies obtained spontaneously or after oocyte donation in our study population was too low to evaluate the obstetrical impact of uterine damage caused by non-TBI regimens. Wider implications of the findings Our results provide strong evidence that a MAC regimen containing high dose of alkylating agents could induce uterine damage. In these sub-group of women, HRT increases the volume of the uterus compared to non-treated women. After TBI, uterine volume is dramatically decreased, with no benefit of HRT on it. Trial registration number NCT 03583294

Outcomes of clostridioides difficile infection in patients with hematopoietic stem cell transplant.

e19054 Background: Hematopoietic stem cell transplantation (HSCT) recipients are at an increased risk for Clostridioides difficile infections (CDI). Despite it being the main cause of nosocomial enterocolitis in this group of patients, diagnosis of CDI remains challenging and carries significant morbidity and mortality. This is usually due to multiple comorbidities, recurrent antibiotics administration, prolonged immunosuppression, and lengthy hospitalization. This study aims to look more into outcomes and predictors of CDI in HSCT patients in terms of incidence, and mortality. Methods: The United States Nationwide Inpatient Sample was used to extract hospitalization data of patients admitted between 2016 to 2019. Using ICD10 revision codes, we identified adults with a discharge diagnosis of CDI and concomitant HSCT. The control group included non-HSCT patients with CDI. The primary outcome was in-hospital mortality. Secondary outcomes were the length of stay (LOS) and hospital charges. Additionally, predictors for developing CDI and dying from CDI were calculated in HSCT patients. Multivariate logistic regression was used to adjust for relevant variables. Results: An estimated 1,235,465 patients were admitted with CDI during the study period. CDI incidence per 100 discharges was higher among HSCT patients at 4.0% vs. 1.0% in the general population. After adjusting for comorbidities and demographic variables, HSCT was independently associated with increased odds of mortality (adjusted odds ratio [AOR] 1.47 (95%CI 1.20-1.80 and P &lt;0.01). Mean length of stay and hospital charges increased by 1.76 days (95%CI 0.90-2.62, P &lt; 0.01) and $59,023 (95%CI $35,940-$82,105, P &lt; 0.01), respectively, in the HSCT group. In the HSCT group, patients with severe liver disease, malnutrition, and graft vs. host disease showed a significantly higher incidence of CDI. Predictors of mortality of HSCT patients and CDI are outlined in the attached table. Conclusions: HSCT recipients are at an increased risk for CDI compared to general population. LOS, total hospital charge, and mortality rate were significantly higher. The risk of CDI was found to be significantly higher in patients with moderate to severe liver disease, graft vs host disease, and malnutrition. The odds of mortality were found to be the highest in patients older than 65 years and those with congestive heart failure, moderate to severe liver disease, graft vs host disease, or malnutrition.[Table: see text]

Impact of TKI combination therapy and MRD negativity on outcomes in Philadelphia chromosome-positive ALL: A retrospective, single-center experience.

e19052 Background: Presence of the Philadelphia chromosome (Ph+) in newly diagnosed B-cell acute lymphoblastic leukemia (ALL) conveys high-risk disease and a poor prognosis. Hematopoietic stem cell transplant (HSCT) following induction and achievement of remission remains the standard of care. In the era of TKIs targeting BCR-ABL1 in addition to newer combination strategies, the impact of HSCT in the first complete remission (CR) remains unclear, particularly in the context of measurable residual disease (MRD) negativity. We present the outcomes of Ph+ B-ALL patients with and without HSCT, stratified with respect to MRD negativity. Methods: We identified 32 patients with Ph+ B-cell ALL from January 2015 to January 2021 at our institution who were treated with TKIs and received HSCT with evaluable MRD prior to transplant. Baseline patient demographics were obtained, including labs, performance status at diagnosis, comorbidities, molecular profiling by NGS, doses of induction, toxicities, response, MRD analysis by PCR, HCT-CI scores, and HSCT outcomes. The event for calculating the overall survival (OS) was the date of death. Patients were otherwise censored at the date of last contact. Results: Of the 25 patients who underwent HSCT, the median age was 46 years and 48.0% were male. TKIs in combination with high-intensity regimens were given in 88.0% of patients at induction. There were no deaths within 60 days following induction. Twenty (80.0%) patients achieved CR or CRi, and of those, 56% were MRD-negative by the time of HSCT. At a median follow-up time of 4.74 years, the OS of patients that achieved CR following induction and HSCT was not reached, and there were no significant differences between the two groups (p = .1326). We then compared the 14 MRD-negative patients undergoing HSCT to 7 MRD-negative patients who did not undergo transplant aged ≤65 years with ECOG ≤2. There was no difference in age (p = .5353), ECOG score (p = .6364), or Charlson Comorbidity Index score (p = .7018) between the two groups. The median OS in the MRD-negative HSCT group was not reached and the median OS in the MRD-negative non-HSCT was 5.45 years (p = .0210). Conclusions: In the era of combination chemotherapy with TKIs, MRD positivity at the time of allogenic HSCT does not appear to impact survival at 5 years in this small retrospective cohort. Post-transplant TKI maintenance may abrogate MRD implications at the time of HSCT. Our findings demonstrate that Ph+ ALL patients benefit from HSCT when candidates, regardless of MRD status, as those undergoing HSCT demonstrated a statistically superior survival. HSCT appears to remain the standard of care despite newer combination strategies and MRD-driven treatment.

Financial incentives to increase stool collection rates for microbiome studies in adult bone marrow transplant patients.

In order to study the role of the microbiome in hematopoietic stem cell transplantation (HCT), researchers collect stool samples from patients at various time points throughout HCT. However, stool collection requires active subject participation and may be limited by patient reluctance to handling stool. We performed a prospective study on the impact of financial incentives on stool collection rates. The intervention group consisted of allogeneic HCT patients from 05/2017-05/2018 who were compensated with a $10 gas gift card for each stool sample. The intervention group was compared to a historical control group of allogeneic HCT patients from 11/2016-05/2017 who provided stool samples before the incentive was implemented. To control for possible changes in collections over time, we also compared a contemporaneous control group of autologous HCT patients from 05/2017-05/2018 with a historical control group of autologous HCT patients from 11/2016-05/2017; neither autologous HCT group was compensated. The collection rate was defined as the number of samples provided divided by the number of time points we attempted to obtain stool. There were 35 allogeneic HCT patients in the intervention group, 19 allogeneic HCT patients in the historical control group, 142 autologous HCT patients in the contemporaneous control group (that did not receive a financial incentive), and 75 autologous HCT patients in the historical control group. Allogeneic HCT patients in the intervention group had significantly higher average overall collection rates when compared to the historical control group allogeneic HCT patients (80% vs 37%, p<0.0001). There were no significant differences in overall average collection rates between the autologous HCT patients in the contemporaneous control and historical control groups (36% vs 32%, p = 0.2760). Our results demonstrate that a modest incentive can significantly increase collection rates. These results may help to inform the design of future studies involving stool collection.

Threshold of Quantitative Cytomegalovirus DNA PCR for Preemptive Treatment in Pediatric Hematopoietic Stem Cell Transplant Recipients.

Consensus cytomegalovirus (CMV) DNA viral load thresholds for intervention in hematopoietic stem cell transplant (HSCT) recipients have not been established, especially in children. This study aimed at obtaining viral load thresholds of CMV DNA to guide preemptive management in pediatric HSCT recipients. A total of 465 blood samples from 177 children who received HSCT between 2015 and 2019 were included in a single center in Korea. The samples were analyzed for CMV infection by both antigenemia assay and quantitative DNA polymerase chain reaction. The 2 assay results were compared for the 233 samples which were collected when antiviral treatment has not been initiated. We determined the viral loads corresponding to the antigenemia of 5 pp65-positive cells/2×10 5 white blood cells (WBCs) as the level for initiating preemptive therapy. Sixty percent of the samples were collected within 100 days (39.7% in 0 to 50 d, 60.2% in 0 to 100 d) from the graft infusion. The correlation between CMV DNA viral load and CMV antigenemia level increased significantly after 50 days from the graft infusion ( r =0.71 vs. r =0.93, P <0.0001). The correlation was greater in the antiviral treatment-naive group than the treatment group ( r =0.75 vs. r =0.66, P <0.0001). Under receiver operating characteristic curve analysis of the treatment-naive group, the estimated threshold CMV DNA viral loads corresponding to 5 pp65-positive cells/2×10 5 WBCs was 898 IU/mL. The CMV DNA levels that corresponded to 5 pp65-positive cells/2×10 5 WBCs was 900 IU/mL in the HSCT group. The proposed viral load thresholds can be used to guide preemptive therapy in pediatric HSCT recipients, especially in the preengraftment period.

Immunological recovery following HLA-matched CD3+ TCR αß+/CD19+ depleted hematopoietic stem cell transplantation in children.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for children with both malignant and nonmalignant diseases. T-cell depletion techniques may result in reduced transplant-related mortality compared with unmanipulated grafts due to a lower incidence of GvHD. Immune recovery and outcome were analyzed in a cohort of 23 patients with malignant and nonmalignant diseases who received CD3+TCRαβ+ T- and B-cell-depleted allografts from matched donors after reduced-intensity or myeloablative conditioning. The median number of CD34+, CD3+TCRαβ+, and CD19+B-cells infused was 12.7×106 /kg, 16.8×103 /kg, and 96×103 /kg bodyweight. With a median follow-up of 36 (range 1-73) months, overall survival and disease-free survival at 3years were 65.2% and 60.8%. Eight patients died, six due to the underlying disease and two of extended visceral cGvHD. Immune reconstitution, disease-free, and overall survivals were similar compared with a historical cohort of 23 patients transplanted with matched unmanipulated bone marrow. A significant lower rate of higher grade (III-IV) aGvHD was observed in the manipulated HSCT group (8.7% vs. 26%; p=0.001), whereas the incidence of cGvHD was equal. Our data suggest that this graft manipulation strategy could be a safe and effective alternative to conventional HSCT techniques in matched donors.

Oral health status after hematopoietic stem cell transplantations: Outcomes from an adult Italian population.

To describe oral cavity changes in patients who underwent a hematopoietic stem cell transplantation (HSCT). A group of 32 patients was studied after a mean period of 48.8 months (±11.22) from HSCT; oral, dental, and periodontal status were collected and compared with those of healthy matched controls. Unstimulated whole salivary flow (UWS) and salivary pH were also measured. A validated questionnaire (EORTC QLQH&N-35) was used for reported quality of life. Fifty-nine percent of patients were affected by chronic graft-versus-host disease (cGVHD). Dental health and periodontal status were statistically worse than in controls (P = .003 and P = .008, respectively). Regarding the HSCT group, UWS was statistically lower, and EORTC QLQH&N-35 significantly higher than those reported in controls (P = .000 for both). There was no statistical correlation between hypo-salivation and conditioning, presence of cGVHD, type of medication used before and after transplantation, and time of follow-up. A reduction in salivary pH has been noted only for patients with erosive oral lesions. The oral cavity of HSCT patients appeared to undergo substantial modifications and the quality of life was deeply compromised.

Clinical Outcomes of B Cell Acute Lymphoblastic Leukemia Patients Treated with Haploidentical Stem Cells Combined with Umbilical Cord Blood Transplantation

Clinical outcomes of hematopoietic stem cell transplantation (HSCT) using a haploidentical stem cell graft and an unrelated umbilical cord blood unit (haplo-cord HSCT) for the treatment of B cell acute lymphoblastic leukemia (B-ALL) remain unclear. This study was conducted to explore the clinical outcomes of haplo-cord HSCT in patients with B-ALL. A total of 112 B-ALL patients who underwent haplo-cord HSCT and 64 B-ALL patients who underwent haploidentical HSCT (haplo-HSCT) at our center between 2010 and 2020 were retrospectively included in this study, and clinical outcomes and prognostic factors were further analyzed. Of the 112 haplo-cord HSCT recipients, 106 (94.6%) achieved complete haploidentical chimerism and 6 (5.4%) had mixed cord blood chimerism. No differences in neutrophil and platelet recovery or in the incidences of graft-versus-host disease, cytomegalovirus/Epstein-Barr virus viremia, bloodstream infection, or hemorrhagic cystitis were observed between the haplo-cord HSCT and haplo-HSCT groups. Compared with the haplo-HSCT group, the haplo-cord HSCT group had a higher absolute number of CD3+ cells (P=.029) and a lower ratio of CD3+CD4+ /CD3+CD8+ cells (P=.049) at 1 month post-transplantation. Moreover, the haplo-cord HSCT group had lower minimal residual disease (MRD) levels at 1 month (P=.020) and 100 days (P=.038) post-transplantation and a better 3-year prognosis (overall survival, P=.016; disease-free survival, P=.041; cumulative incidence of relapse [CIR], P=.016). The CIRs in patients with adverse genomic features (P=.040) or flow cytometry-based MRD (FCM-MRD) ≥1×10-4 (P=.033) were improved by haplo-cord HSCT. Multivariate analysis revealed that haplo-cord HSCT could independently improve the 3-year OS, DFS, and CIR of B-ALL patients (OS, P=.029; DFS, P=.024; CIR, P=.024). In addition, allo-HSCT at first complete remission was an independent parameter associated with 3-year OS for B-ALL patients (P=.014). An FCM-MRD ≥1×10-4 pre-HSCT could independently predict unfavorable 3-year DFS and CIR (DFS, P=.020; CIR, P=.036) in B-ALL patients. Our data suggest that the use of haplo-cord HSCT can independently improve survival in patients with B-ALL.

Chemotherapy with the Use of TKIs Based on MRD Has the Potential to Avoid Hematopoietic Stem Cell Transplantation in Treatment for Children with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL). Results of the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) Study ALL-Ph13

Aims: Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) patients generally have a poor prognosis when treated with chemotherapy alone. In adults, allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission is still the standard strategy for Ph+ALL. However, in children, HSCT should be avoided as much as possible to eliminate late complications. There are some reports showing that the combination of tyrosine kinase inhibitors (TKIs) with chemotherapy may avoid HSCT in childhood Ph+ALL. Thus, we planned this clinical trial (JPLSG ALL-Ph13) with the aim of improving outcomes with as few HSCT by chemotherapy with TKIs based on Ig/TCR minimal residual disease (MRD).Methods: Patients aged 1 to 19 with Ph+ALL were enrolled in JPLSG ALL-Ph13 Study. The diagnosis of Ph+ALL was performed using reverse-transcription PCR for BCR-ABL1. Chemotherapy follows the BFM ALL high-risk regimen (IA, IB, HR3, HR2, HR1, III, IM, III, IM, III, and maintenance). Imatinib was started on day 15 of induction therapy and continued until the final day of maintenance therapy (Ima group). If Ig/TCR MRD was positive (≥10 -4) at the end of IB, imatinib was changed to dasatinib and chemotherapy was continued (Dasa group). If MRD was positive at the end of the HR blocks, HSCT was performed (HSCT group).Results: During the period 2013-17, 43 patients were registered in this study, and 2 patients were excluded by not meeting inclusion criteria. Thirty-three, 7, and 1 patient were stratified into Ima, Dasa, and HSCT groups, respectively. Induction rate was 52.6% at the end of IA and 89.2% at the end of IB. MRD-negative rate was 61.3% at the end of IB and 87% at the end of HR. Although 51.2% of patients eventually received HSCT, only 13.9% received HSCT at the first complete remission. In all patients, the 3-year event-free survival (EFS) rate was 65.1%, and the 3-year overall survival (OS) rate was 85.1%. Four patients died of serious infections during treatment (2 in IA, 2 in 1st III).Interpretation: In our previous study for children with Ph+ALL (the JPLSG Ph+ALL04 study), all patients underwent HSCT, with the 3-year EFS rate of 57% and the OS rate of 80%. In this ALL-Ph13 study, the EFS and OS are almost the same as those in the Ph+ALL04. These are also almost the same as those in the EsPhALL2010 study, which aimed at avoiding HSCT. However, as in the EsPhALL2010 study, the comparatively high incidence of fatal adverse events was a problem with this study.Conclusion: Chemotherapy with the use of TKIs based on MRD has the potential to avoid HSCT in treatment for children with Ph+ALL. Reducing the occurrence of fatal adverse events is a future challenge to overcome. DisclosuresNo relevant conflicts of interest to declare.

Serum anti-Müllerian hormone as a marker of ovarian reserve after cancer treatment and/or hematopoietic stem cell transplantation in childhood: proposal for a systematic approach to gonadal assessment.

Female patients treated with alkylating agents in childhood are at risk for ovarian impairment. We aimed at describing the pattern of residual ovarian function in a cohort of survivors of hematological malignancies and/or hematopoietic stem cell transplantation (HSCT) and assessing the relationship between cyclophosphamide equivalent dose (CED) and anti-Müllerian hormone (AMH). Gonadal health was clinically and biochemically assessed in 124 post-menarchal survivors who underwent treatment for pediatric hematological malignancies and/or HSCT between 1992 and 2019. Overt 'premature ovarian insufficiency' (POI) was detected in 72.1 and 3.7% of transplanted and non-transplanted patients, respectively; milder 'diminished ovarian reserve' (DOR) in 16.3 and 22.2%. In non-transplanted patients, increasing CED values were associated with lower AMH-SDS (P = 0.04), with the threshold of 7200 g/m2 being the best discriminator between DOR/POI and normal ovarian function (AUC: 0.75 on ROC analysis) and with an observed decrease of 0.14 AMH-SDS for each CED increase of 1 g/m2. In addition, age at diagnosis ≥10 years played a detrimental role on ovarian reserve (P = 0.003). In the HSCT group, irradiation was associated with a statistically significant reduction in AMH-SDS (P = 0.04). In non-transplanted patients, CED ≥ 7200 mg/m2 was associated with a DOR, while younger age at diagnosis played a protective role on ovarian reserve. As a result of the data collected, we propose a systematic algorithm to assess iatrogenic gonadal impairment in young female patients exposed to chemo-radiotherapy in childhood for hematological disorders.

Decrease in Mortality from Sepsis: Impact of the Multidisciplinary Program for the Hematologic Patient at Very High Risk.

A program for the hematologic patient at very high risk of infections (HAR, from its initials in Spanish) was implemented, based on a multidisciplinary team and six measures intended to reduce the colonization and subsequent sepsis by multidrug-resistant organisms (MDRO). We aimed at evaluating the effectiveness of the HAR program in terms of MDRO infections mainly caused by Klebsiella pneumoniae carbapenemase-producing and multidrug-resistant Pseudomona aeruginosa, and sepsis-related mortality. We established retrospective comparisons between the pre-HAR period (2016-2018) and the post-HAR period (2018-2019), in patients who received a hematopoietic stem cell transplant (HSCT) and/or intensive chemotherapy to treat non-M3 acute myeloid leukemia (CH-AML). We included 262 patients: 176 pre-HAR and 86 post-HAR. MDRO infection was 4.6% at 30days and 6.1%at 90days (all the cases during the pre-HAR period). Sepsis-related mortality was 6.5%, considering a median follow-up of 608days: 6.1% in the HSCT group and 12.4% in the CH-AML group (p = 0.306). Sepsis-related mortality was 8.7%in the pre-HAR period and 0% in the post-HAR period (p = 0.014). The implementation of this multidisciplinary program based in preventive measures and the appropriate use of antibiotics enabled a decrease in sepsis-related mortality in very high-risk hematologic patients.

The Role of Upfront Hematopoietic Stem Cell Transplantation (HSCT) in Peripheral T-Cell Lymphoma (PTCL) Patients in Complete Remission (CR) with a Special Focus on Nodal PTCL: Report from the Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE), a Prospective Multicenter Cohort Study

The Role of Upfront Hematopoietic Stem Cell Transplantation (HSCT) in Peripheral T-Cell Lymphoma (PTCL) Patients in Complete Remission (CR) with a Special Focus on Nodal PTCL: Report from the Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE), a Prospective Multicenter Cohort Study

Primary Plasma Cell Leukemia in China: A Retrospective Single Center Study

Background: Primary plasma cell leukemia (PPCL) is a rare and aggressive malignancy, with a peculiar clinical and biological features and very poor prognosis. It differs from secondary PCL (SPCL), a leukemic transformation from a previously diagnosed multiple myeloma (MM). Although a few studies have suggested that use of novel agents and performing autologous stem cell transplantation (ASCT) has prolonged survival time of PPCL patients, the prognosis is still poor compared with MM, and the optimal therapy remains unclear.Materials and methods: 50 patients with PPCL were enrolled in Blood Diseases Hospital, Chinese Academy of Medical Sciences in China from June 1999 to June 2016. We analyzed the clinical and cytogenetic characteristics of these patients, survival analysis was conducted by Kaplan-Meier estimates and compared using the log-rank test.Results: Median age of 50 cases was 58 years (range between 26 and 86 years), 76% patents were less than 60 years old. There were 34 males and 16 females. The most common immunoglobulin type was IgG (42%), 26% of patients had light chain type. Regarding the ISS, 2 (4.0%) patients were stage I, 7(14.0%) were stage II, and 41 (82.0%) were stage III. 44 patients (88%) was diagnosed with anemia, 5(10%)patients were found leukopenia, while 23 (46%) patients with leukocytosis. 38(76.0%) patients had thrombocytopenia at diagnosis. 14 (28%) patients were found with renal dysfunction. 42(84%) patients showed elevated LDH level.39 (78%) patients had high β-2microglobulin levels (> 5.5 mg/L). 20(40.0%) patients had low serum albumin levels (< 3.5 g/dL) . There were 33(66.0%) patients with hypercalcemia. Organomegaly (liver, spleen and etc.) was detected in 25 (50.0%) patients and osteolytic bone lesions were present in 34(68.0%) patients. 8(16.0%) patients were involved in extramedullary disease.Cytogenetic analysis has showed that the most common abnormalities were complex karyotype (58.3%), while 50% patients with hypodiploid were found in 24 cases. FISH analysis showed that 13 patients with del13q, 15 patients with del17p, and 6 patients with t(4;14), while 12 patients with t(11;14). 14 patients were found at least 2 abnormalities of 30 patients.All patients were treated in our hospital, 36 cases were treated with novel agent-based chemotherapy , such as bortezomib, cyclophosphamide, and dexamethasone(BCD), or bortezomib, doxorubicin, and dexamethasone (PAD), or thalidomide, melphalan, and prednisolone (MPT), or thalidomide ,cyclophosphamide, dexamethasone (TCD), or thalidomide and dexamethasone (TD), or bortezomib,dexamethasone,cis-platin,doxorubicin,cyclophosphamide,etoposide (VDPACE).8 patients were treated with conventional chemotherapy including vincristine, doxorubicin, and dexamethasone(VAD), or cyclophosphamide, etoposide, dexamethasone(CED), or melphalan and prednisolone(MP), or M2 regimen. 6patients received hematopoietic stem cell transplantation (HSCT) after initial induction chemotherapy, 4 of them received ASCT, 2 patients with allogeneic stem cell transplantation (allo-SCT).Three patients achieved complete remission (CR), while 6 patients received very good partial remission (VGPR) after novel agent therapy. In the conventional chemotherapy group, only one patient received VGPR, and 3 patients received partial remission (PR). In the HSCT group, there were one with CR, and 2 patients with VGPR. Overall response rates (ORR) were significantly higher in patients with novel agent-based regimens compared with those treated with conventional chemotherapy (72% vs. 50%, P < 0.05). (Table 3)Take the total cohort as a whole, the median PFS and OS were 6 months (95% CI 0-15.67), and 12 months (95% CI 5.08-18.09). In total, 5 (10%) patients died within less than 1 month. The major causes of early mortality were disease progression and infection. The median OS was lower in patients who were initially treated with conventional agents (12 months, 95%CI 0-26.4) compared with those treated with novel agents (24 months, 95% CI 8.9-39.5, P = 0.15), but the difference was not statistically significant. Additionally, patients with complex karyotypes showed a trend with poor survival compared to those with normal one.Conclusion: Plasma cell leukemia has a higher incidence in cytogenetic aberrations. Novel agent-based chemotherapy combined with SCT could deepen the response rate, and improve the survival time. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Long Term Follow up after Adoptive Transfer of CD19-Specific CAR+ T Cells Genetically Modified Via Non-Viral Sleeping Beauty S ystem Following Hematopoietic Stem Cell Transplantation (HSCT)

BACKGROUND. We evaluated a human application of T cells genetically modified using the Sleeping Beauty (SB) transposon/transposase system to express a CD19-specific chimeric antigen receptor (CAR, designated CD19RCD28). The SB system uses a synthetic DNA transposon for nonviral somatic gene transfer. The initial data were reported (J Clin Invest. 2016 Sep 1;126(9):3363-76) and we now present long-term follow-up (LTFU).METHODS. T cells were genetically modified using DNA plasmids from the SB platform to stably express CD19RCD28 and selectively propagated ex vivo with activating and propagating cells (AaPC) with cytokines. Twenty-six patients with advanced non-Hodgkin lymphoma (n=9) or acute lymphoblastic leukemia (n=17) underwent autologous (n=7) or allogeneic (n=19) HSCT followed by a T-cell infusion as adjuvant therapy on two clinical trials NCT00968760 and NCT01497184, respectively. Patients were subsequently enrolled onto a LTFU study, NCT01492036, to be followed for up to 15 years. During this time, patients could be tested annually for the persistence of genetically modified T cells using PCR and flow cytometry.RESULTS. The persistence of SB-modified T cells was measured in two of the seven autologous HSCT/CAR+T patients as long as 4-years post infusion and both remain progression-free. Similarly, CAR expression was detected in three allogeneic HSCT recipients one-year post T-cell infusion with no disease progression. Upon LTFU of the autologous HSCT group, six of seven patients continue in complete remission (CR) at a median of 3.4 years (range: 1.7 to 4.2 years). The 3-year progression-free (PFS) and overall survival (OS) rates are 86% and 100%, respectively (Figure). After allogeneic HSCT, recipients received donor-derived CAR+ T cells (8 haploidentical, 10 matched-sibling, one 1Ag-mismatched sibling). For this allogeneic group, six patients remain alive and in CR following haplo (n=4) or matched sibling donor (n=2) HSCT with a median follow-up of 1.5 years (range: 0.003 to 2.9 years). The 2-year PFS and OS rates are 45% and 49%, respectively (Figure). Additionally, the 2-year PFS and OS rates for haplo-identical transplants were 57% and 71%, respectively. No long-term safety issues were identified; specifically, no graft failure or excess graft-versus-host-disease.CONCLUSIONS. CD19-specific CAR+ T cells could be detected and were well-tolerated years after adoptive transfer and appear to provide long-term cancer control when infused after HSCT for patients with advanced disease. These encouraging results support further clinical development of this non-viral gene therapy approach.Figure: Overall and progression-free survivals of recipients of SB-modified CAR+ T cells after autologous and allogeneic HSCT. [Display omitted] DisclosuresHuls:Former employee of Intrexon: Employment. De Groot:Ziopharm: Employment. Smith:Ziopharm: Employment. Yang:Ziopharm: Employment. Kantarjian:Bristol-Meyers Squibb: Research Funding; Novartis: Research Funding; Delta-Fly Pharma: Research Funding; Amgen: Research Funding; ARIAD: Research Funding; Pfizer: Research Funding. Cooper:Immatics: Equity Ownership, Patents & Royalties, Research Funding; Intrexon Corporation: Equity Ownership, Patents & Royalties; Sangamo Biosciences: Patents & Royalties; Organovo Holdings: Equity Ownership; Ziopharm: Employment, Equity Ownership, Research Funding; Procter & Gamble: Equity Ownership; Miltenyi Biotec: Honoraria; Ampliphi Biosciences: Equity Ownership; Argos Therapeutics: Equity Ownership; Ferring: Consultancy; Targazyme, Inc.: Equity Ownership.

Outcomes of Adults with Acute Lymphoblastic Leukemia (ALL) Following Relapse After First Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

AbstractAbstract 4215 Background:Outcomes of SCT in adult ALL have improved over the past decade. However, for patients (pts) who relapse after SCT, the prognosis is poor and treatment options are limited; the clinical course and prognostic factors affecting these pts are not well characterized. Methods:We retrospectively analyzed the outcomes of relapsed adult ALL pts who underwent first SCT between 1993–2011. The objectives of the study were to assess outcome after salvage therapy in these pts and to investigate the prognostic factors affecting outcome. Out of 365 ALL pts who underwent first SCT, 123 pts relapsed and received further treatment. Outcome was assessed since the date of relapse until death or last follow-up. Results:The median time to relapse was 4.4 months (mo.) (0.4–38.5 mo.) from first SCT. With a median follow up of 11 mo. (0.1 mo. -9 years) from time of relapse, the actuarial OS at 6 mo. was 35% (27–44%). First salvage treatments and median OS after relapse were: second SCT (n=19, OS 10 mo.) or donor lymphocyte infusion (DLI) (n=11, OS 6.5 mo.) with or without prior chemotherapy, radiation therapy for extramedullary only relapse (n=6, OS 3 mo.), cytoreductive chemotherapy (n=30, OS 4 mo.), mild chemotherapy (n=27, OS 4 mo.) and palliative care (n=23, OS 1 mo.). Mild chemotherapy was defined as combinations of steroids and vincristine, single cytotoxic agents such as clofarabine or nelarabine, tyrosine kinase inhibitors, hypomethylating agents, or monoclonal antibody therapies. Seven pts were lost to follow-up. Following the first salvage treatment, 47 pts (38%) went into complete remission (CR). The CR rate was higher in the HSCT, radiotherapy and DLI groups (84%, 83% and 64% respectively) compared with the mild chemotherapy (41%) and cytoreductive chemotherapy (27%) groups.In a univariate analysis for survival (Table 1), adverse factors included active disease at time of first SCT and short time to relapse from first SCT (<6 mo.). In pts who were not in active disease at SCT (n=83), the EBMT prognostic score (Spyridonidis et al, Leukemia 2012) was found to be highly prognostic of OS. Patients with 2/3 adverse factors (first SCT at CR2/3, relapse in <6.9 mo. and peripheral blast >10% at relapse) had significantly worse 6-mo. OS compared to pts with 0/1 adverse factor (p=0.009). Presence of isolated extra-medullary relapse was not associated with improved OS compared to pts with systemic relapse.Second SCT was found to be correlated with improved outcome compared with cytoreductive chemotherapy (p=0.003). Among the pts who received treatment and were evaluable for response (n=86), achievement of CR after first salvage was the most significant predictor of survival (p=0.001). In bivariate analysis, this benefit was shown to be independent of performing second SCT. Conclusion:Prognosis of ALL pts who relapse following SCT remains poor. However, second SCT may allow long term survival in a small subset of pts. Longer time to progression after first SCT and successful induction of CR following first salvage treatment are associated with improved survival post relapse. We corroborated the EBMT prognostic score for pts experiencing relapse after HSCT.Table 1Univariate analysis of factors influencing 6-month post relapse OSCovariatesN (123)HR95% CIP valueAge at HSCT (years)<=3055Ref.>30680.70.5–1.10.2SexFemale39Ref.Male841.71.01–2.80.05LineageB-cell85Ref.T-cell2810.6–1.70.99CytogeneticPh-71Ref.Ph+280.70.4–1.30.2Status at HSCTCR120Ref.PIF/CR2/CR3632.020.9–4.30.07Active disease403.11.4–6.70.005Preparative regimenRIC32Ref.HD911.10.6–1.80.8AllotypeMatched unrelated45Ref.Matched related650.70.5–1.20.2Cord blood70.80.3–2.20.6Haploidentical61.60.6–4.20.3Time to relapse (months)>642Ref.<=6812.051.2–3.40.007Site of relapseSystemic99Ref.Isolated extramedullary240.80.4–1.40.4First line salvage*Cytoreductive chemotherapy30Ref.Second SCT190.20.1–0.60.003Chemotherapy + DLI110.50.2–1.30.1Mild chemotherapy270.990.5–1.90.9Radiation therapy only60.90.3–3.10.9Response to first salvage**CR47Ref.NR392.91.6–5.40.001CR indicates complete remission; PIF, primary induction failure; RIC, reduced intensity conditioning; HD, high dose conditioning; NR, no response.*Palliative group was excluded.**Palliative group and non-evaluable pts excluded. Disclosures:No relevant conflicts of interest to declare.

TREATMENT AND OUTCOMES OF PATIENTS WITH POST‐TRANSPLANT LYMPHOPROLIFERATIVE DISORDER: A SINGLE CENTRE EXPERIENCE

Background: Post-transplant lymphoproliferative disorder (PTLD) is a potentially severe complication that takes place after solid (SOT) or allogeneic hematopoietic stem cell transplant (HSCT). To date, its treatment is not standardised, and choice of therapy depends on histology and clinical presentation. We report the results of a 10 years (yrs) single-centre retrospective study assessing presentation, treatment patterns and outcomes of patients with PTLD. Methods: Patients ≥18 yrs diagnosed with a PTLD between 2011 and 2020 were identified in our medical records database. Primary endpoints were 2 yrs progression-free survival (PFS), overall survival (OS), and relapse incidence (RI) estimated with Kaplan-Meier and comparison between HSCT and SOT group. Secondary endpoints were the overall response rate (ORR) and complete response rate (CRR) at the end of first line treatment. Exploratory univariate analysis for OS, PFS were investigated using Cox regression model. Results: A total of 38 patients were included. Patient's characteristics and treatment strategies are presented in Table 1. HCST patients present a significantly higher prevalence of early onset PTLD (90% in HCST group vs 0% in SOT group), positive EBER immunostaining (100% vs 22%) and detectable Epstein Bar Virus (EBV) viremia (100% vs 28%), higher LDH (95% vs 66%), IPI score 3-5 (50% vs 33%), with a remarkable higher use of single agent Rituximab as first line therapy in HSCT patients (65% vs 11%). 2 yrs PFS was 54% (95%CI 36-73%) for the entire cohort, 42% (95%CI 16-67%) for HSCT and 67% (95%CI 41-92) for SOT; p-value 0.23. 2 yrs OS was 53% (95%CI 41-66%) for the entire cohort, 42% (95% CI 16-67%) for HSCT and 65% (95% CI 39-91) for SOT; p-value 0.22. 2 yrs RI was 9% (95% CI: 0-21%) for the entire cohort, 0% for HSCT and 14% (95% CI 0-33%) for SOT; p-value 0.26. ORR and CRR were similar with 82% (75% for HSCT, 89% for SOT, p-value 0.41) at the end of first line treatment. High IPI score (3-5) demonstrated worse outcome for PFS (HR: 2.5, 95%CI 0.95-6.65, p-value 0.063) and OS (HR: 2.4, 95%CI 0.92-6.48, p-value 0.07). A total of 17 patients died during follow-up: 7 during first line treatment of PTLD complication and multiorgan failure (5 in the HSCT group, 2 in the SOT group; p-value 0.41); 2 following PTLD relapse after first CR (0 in the HSCT group, 2 in the SOT group; p-value 0.22). Conclusion: This study highlights the clinical and therapeutic heterogeneity of PTLD. We observe a worse 2 yrs PFS and OS in patients with high IPI score. CRR after first line treatment is almost 90% in the SOT group, with a 2 yrs OS of 53%, consistent with previous studies (Trappe et al, JCO 2017). The higher mortality observed in the HSCT group suggests that serious treatment-related toxicities remain main challenges in this fragile patient population. New tools to guide therapeutic approaches in PTLD patients are warranted. Keywords: Lymphoid Cancers - Other No conflicts of interests pertinent to the abstract.