Rocio Parody

Background: Transformation of follicular lymphoma into an aggressive lymphoma (tFL) worsens the prognosis and the standard treatment is not completely defined. Allogeneic hematopoietic stem cell transplantation (alloSCT) could be a potentially curative option for these patients, but it has not been widely explored. Methods: We designed a retrospective multicenter study to analyze the efficacy and toxicity of alloSCT in tFL patients and potential prognostic factors of survival. Results: A total of 43 patients diagnosed with tFL who underwent alloSCT in 14 Spanish centers between January 2000 and January 2019 were included. Median age was 44 (31–67) years. After a median follow-up of 58 months, estimated 5-year overall survival (OS) and progression-free survival (PFS) were both 35%. Estimated 100-day and 1-year non-relapse mortality (NRM) were 20% and 34%, respectively. The type of conditioning regimen (3-year OS of 52% vs. 20%, respectively, for reduced-intensity vs. myeloablative conditioning) and development of chronic graft versus host disease (cGVHD) (3-year OS of 75% vs. 40%) were the only factors significantly associated with OS. The only variable with an independent association with OS was cGVHD (HR, 3.4; 95% CI, 1.2–9.6). Conclusions: Our results indicate that alloSCT continues to be a potentially curative option for patients with tFL.

Allo-SCT is a curative option for selected patients with relapsed/refractory (R/R) MCL, but with significant NRM. We present the long-term results of patients receiving allo-SCT in Spain from March 1995 to February 2020. The primary endpoints were EFS, OS, and cumulative incidence (CI) of NRM, relapse, and GVHD. We included 135 patients, most (85%) receiving RIC. After a median follow-up of 68 months, 5-year EFS and OS were 47 and 50%, respectively. Overall and CR rates were 86 and 80%. The CI of relapse at 1 and 3 years were 7 and 12%. NRM at day 100 and 1 year were 17 and 32%. Previous ASCT and Grade 3–4 aGVHD were associated with a higher NRM. Grade 3–4 aGVHD, donor type (mismatch non-related), and the time-period 2006–2020 were independently related to worse EFS. Patients from 1995–2005 were younger, most from HLA-identical sibling donors, and were pretreated less. Our data confirmed that allo-SCT may be a curative option in R/R MCL with low a CI of relapse, although NRM is still high, being mainly secondary to aGVHD. The arrival of new, highly effective and low toxic immunotherapeutic or targeted therapies inevitably will relegate allo-SCT to those fit patients who fail these therapies, far away from the optimal timing of treatment.

Traceability of patients who are candidates for Hematopoietic cell transplant (HCT) is crucial to ensure HCT program quality. Continuous knowledge of both a detailed registry from a HCT program and final exclusion causes can contribute to promoting a real-life vision and optimizing patient and donor selection. We analyzed epidemiological data reported in a 4 year-monocentric prospective registry, which included all patients presented as candidates for autologous (Auto) and/or allogeneic (Allo) HCT. A total of 543 patients were considered for HCT: 252 (42.4%) for Allo and 291 (57.6%) for Auto. A total of 98 (38.9%) patients were excluded from AlloHCT due to basal disease progression more commonly (18.2%). Seventy-six (30.2%) patients had an HLA identical sibling, whereas 147 (58.3%) patients had only Haplo. UD research was performed in 106 (42%) cases, significantly more often in myeloid than lymphoid malignancies (57% vs 28.7%, p < 0.001) but 61.3% were finally canceled, due to donor or disease causes in 72.4%. With respect to Auto candidates, a total of 60 (20.6%) patients were finally excluded; progression was the most common cause (12%). Currently, Haplo is the most frequent donor type. The high cancellation rate of UD research should be revised to optimize further donor algorithms.

The Endothelial Activation and Stress Index (EASIX) is a laboratory-based prognosis index defined as creatinine × lactate dehydrogenase/platelets. When measured at pretransplantation evaluation (EASIX-PRE), it predicts allogeneic hematopoietic cell transplantation (alloHCT) mortality. This study explores its ability to predict intensive care unit (ICU) admission and validates EASIX-PRE predictive power for overall survival (OS) and nonrelapse mortality (NRM) in 167 consecutive patients undergoing alloHCT. EASIX-PRE was calculated retrospectively in all patients and transformed into log2 values (log2-EASIX-PRE). Log2-EASIX-PRE predicted ICU admission (hazard ratio [HR], 1.41; P < .001), OS (HR, 1.19; P = .011), and NRM (HR, 1.28; P = .004). The most discriminating EASIX-PRE cutoff value for risk of ICU admission was the 75th percentile (2.795); for OS and NRM, it was the median value (1.703). Patients with EASIX-PRE >2.795 had higher incidence of ICU admission in comparison with patients with lower EASIX-PRE values (day +180, 35.8% vs 12.8%; HR, 2.28; P = .010). Additionally, patients with EASIX-PRE >1.073 had lower OS (2 years, 57.7% vs 68.7%; HR, 1.98; P = .006) and higher NRM (2 years, 38.7% vs 18.5%; HR, 2.92; P = .001) than patients with lower EASIX-PRE results. Log2-EASIX-PRE was not associated with incidence of transplantation-associated microangiopathy, sinusoidal obstruction syndrome, or acute graft-versus-host disease. This study proposes EASIX-PRE as a prognostic tool to identify patients undergoing alloHCT at increased risk of severe organ dysfunction and who would therefore require ICU admission. Early identification of patients at high risk of severe events could contribute to personalized intervention design. Additionally, it validates the association between EASIX-PRE and OS and NRM in those undergoing alloHCT.

Introducing post-transplant, cyclophosphamide (PT-Cy) graft-versus-host disease (GVHD) prophylaxis in the setting of haploidentical donor transplantation has marked the most important advance in allogeneic hematopoietic cell transplantation (alloHCT) within the past 15 years. The efficacy of this procedure and its simple features have allowed for the significantly widespread application of alloHCT worldwide. Indeed, the procedure’s effectiveness in reducing immunological complications in the haploidentical setting has even challenged the status quo use of calcineurin-inhibitor, methotrexate-based GVHD prophylaxis in the setting of HLA-identical donors. Currently, however, prospective clinical trials in support of PT-Cy-based GVHD prophylaxis in the HLA-matched setting are striving to resolve the matter of its potential role. This review will briefly report the overall outcomes of PT-Cy-based GVHD prophylaxis in the haploidentical setting and summarize results obtained in the HLA-identical field. We will present future perspectives at the end of the manuscript.

Background: Patients who have recently received a hematopoietic cell transplant (HCT) are at higher risk of acute complications in the first weeks after discharge, especially during the COVID-19 pandemic. Objective: The aim of this study was to test the use of a telehealth platform for the follow-up of HCT patients during the first two weeks after discharge. Methods: In total, 21 patients who received autologous or allogeneic HCT for hematological malignancies were screened from April 30, 2020, to July 15, 2020. The telehealth platform assisted in the daily collection of vital signs as well as physical and psychological symptoms for two weeks after hospital discharge. The required medical devices (oximeter and blood pressure monitor) were given to patients and a dedicated smartphone app was developed to collect this data. The data were reviewed daily through web-based software by a hematologist specializing in HCT. Results: Only 12 of 21 patients were able to join and complete the study. Technological barriers were the most frequent limiting factor in this study. Among the 12 patients who completed the study, adherence to data reporting was high. The patients’ experience of using such a system was considered good. In two cases, the system enabled the early recognition of acute complications. Conclusions: This pilot study showed that telehealth systems can be applied in the early posttransplant setting, with evident advantages for physicians and patients for both medical and psychological aspects. Technological issues still represent a challenge for the applicability of such a system, especially for older adult patients. Easier-to-use technologies could help to expand the use of telehealth systems in this setting in the future.

BACKGROUND Patients who have recently received a hematopoietic cell transplant (HCT) are at higher risk of acute complications in the first weeks after discharge, especially during the COVID-19 pandemic. OBJECTIVE The aim of this study was to test the use of a telehealth platform for the follow-up of HCT patients during the first two weeks after discharge. METHODS In total, 21 patients who received autologous or allogeneic HCT for hematological malignancies were screened from April 30, 2020, to July 15, 2020. The telehealth platform assisted in the daily collection of vital signs as well as physical and psychological symptoms for two weeks after hospital discharge. The required medical devices (oximeter and blood pressure monitor) were given to patients and a dedicated smartphone app was developed to collect this data. The data were reviewed daily through web-based software by a hematologist specializing in HCT. RESULTS Only 12 of 21 patients were able to join and complete the study. Technological barriers were the most frequent limiting factor in this study. Among the 12 patients who completed the study, adherence to data reporting was high. The patients’ experience of using such a system was considered good. In two cases, the system enabled the early recognition of acute complications. CONCLUSIONS This pilot study showed that telehealth systems can be applied in the early posttransplant setting, with evident advantages for physicians and patients for both medical and psychological aspects. Technological issues still represent a challenge for the applicability of such a system, especially for older adult patients. Easier-to-use technologies could help to expand the use of telehealth systems in this setting in the future.

Introduction: Therapy-related myeloid neoplasms (t-MNs) account for about 10 to 20% of all cases of AML and MDS. Allogenic hematopoietic cell transplantation (allo-HCT) is considered as the only curative treatment in this high-risk setting. Given the rise of long-term cancer survivors, an increasing number of patients are expected to become transplant candidates. Physicians are concerned about the frailty and the risk of recurrence of primary cancer. In this retrospective registry-based study, we focused on patients with t-MN secondary to breast cancer radio- and/or chemotherapy, and collected information about the outcomes and complications after allo-HCT. Methods and results: In the EBMT registry we identified 252 female adult patients who underwent an allo-HCT between 2006 and 2016 for t-MN secondary to breast cancer treatment. Median age at transplantation was 57 years, and the median time from the breast cancer diagnosis to t-MN diagnosis and subsequent allo-HCT were 3.7 and 4.6 years, respectively. The indication for allo-HCT was AML and MDS in 77% and 23% of cases, respectively. Sixty-seven% of patients were in complete remission (CR) of their t-MN at the time of transplant. Abnormal karyotype was recorded in 40% of cases. A reduced Karnofsky performance status (KPS<90) was noted in 29% of cases, and 44% of patients presented with at least one comorbidity other than the primary malignancy. Stem cell source was peripheral blood in 89% of cases. Conditioning regimens were reduced-intensity (RIC) in 61% and myeloablative (MAC) in 39% of patients, respectively, and in vivo T-cell depletion was applied in 55% of cases. TBI was used in 18%. Thirty-nine% of donors were matched related (MRD), and 30% matched unrelated (MUD). For the breast cancer, at the time of diagnosis, 5% presented with distant metastasis and 15% were triple negative; 86% received chemotherapy and 88% radiotherapy, 72% both. Of note, at the time of transplant, 93% of patients were deemed in first CR of their breast cancer, and additional 5% were in second CR or more: data on remission status were missing for 57 of patients. Median follow-up from transplant was 20 months and for the entire cohort the 2-year overall survival (OS) was 50% (95%CI 44-56%): in univariate analysis (UVA), an abnormal karyotype, being transplanted not in CR for the hematological malignancy and a worse KPS were associated with a worse prognosis [2-year OS: 41% (28-53%) for abnormal karyotype, 52% (42-62%) for normal, p=.035; 57% (49-64%) for CR, 56% (23-88%) for untreated, 34% (23-45%) for not in CR, p=.002; 55% (47-63%) for KPS≥90, 43% (31-55%) for KPS<90, p=.05]. The 2-year relapse-free-survival (RFS) was 45% (39-52%): as observed for the OS, a detrimental effect on RFS was observed for abnormal karyotype [2-year RFS: 34% (22-46%) for abnormal, 49% (39-59%) for normal karyotype, p=.034] and not being transplanted in remission for the t-MN [52% for CR (44-59%), 44% for untreated (12-77%), 31% (20-42%) for not in CR, p=.002]. 2-year relapse incidence and NRM were 33 (27-39%) and 22% (17-27%), respectively. An abnormal karyotype was significantly associated with a higher relapse rate compared to a normal [50 (37-62%) vs 26% (17-34%), p<0.001], as did an uncontrolled t-MN at the time of transplant [27% (20-34%) for CR, 33% (3-64%) for untreated, 47% (35-59%) for not in CR, p<.001]. Patients pre-exposed to radiotherapy for breast cancer experienced a higher relapse rate compared to those who did not [35 (28-43%) vs 17% (2-33%), p=.04], while the NRM was lower [18 (12-24%) vs 38% (19-58%), p=.02]. Acute grade II-IV GVHD occurred in 26% (22-33%) of patients, and the 2-year incidence of chronic GVHD was 41% (35-47%) including 22% (17-27%) of extensive grade. Seventeen cases of breast cancer recurrence were observed, of which 13 invasive. A curative approach was adopted in 7 cases. The most frequent cause of death in the whole cohort was relapse of t-MN (36%), followed by infection (28%) and GVHD (16%): the relapse of the primary breast cancer accounted for 10 (7%) cases of death. Conclusions: Our study shows that allo-HCT can be safely performed in patients with t-MN secondary to treatment to breast cancer. A major drawback is the relapse of the primary disease which nevertheless appeared a rare event. Tight collaboration and multidisciplinary discussion between the oncologist and the hematologist are fundamental, and an adequate follow-up for the solid malignancy is essential thereafter. Figure 1 Disclosures Ganser: Novartis: Consultancy; Celgene: Consultancy. Scheid:Takeda: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Amgen: Honoraria; Janssen: Honoraria, Research Funding; BMS: Honoraria. Yakoub-Agha:Celgene: Honoraria; Novartis: Honoraria; Gilead/Kite: Honoraria, Other: travel support; Janssen: Honoraria; Jazz Pharmaceuticals: Honoraria.

Introduction Biosimilars of granulocyte colony-stimulating factors (G-CSF) have shown similar efficacy to originator filgrastim (Neupogen® [NEU]; Amgen Inc.) as prophylaxis in neutropenia and in the mobilization of stem cells in patients receiving combination chemotherapy with G-CSF. Methods This was a retrospective study in which the characteristics of stem cell mobilization treated with a G-CSF alone were compared in 216 patients and 56 donors. The two G-CSF compared were NEU and the biosimilar filgrastim Zarzio® (Sandoz GmbH) (referred to hereafter as BIO). Primary objectives were mobilization rate (minimum of 10 × 10³/ml CD34+ on day 4 of treatment [day +4]) and use of the immunostimulant plerixafor (PLEX) in each group. Results The general characteristics of the patients receiving NEU (n = 138) and those receiving BIO (n = 78) did not differ significantly. PLEX was used in 24% of BIO patients and in 25.7% of NEU patients. The median CD34+ cell count on day +4 was significantly lower in BIO patients who needed PLEX than in those who did not (2.4 vs. 4.8 × 10³/ml; p = 0.002), as was the final CD34+ cell count (2.5 vs. 3.3 × 10⁶/kg; p 0.03). Mobilization failure rate was higher in the BIO group than in the NEU group (20 vs. 0%; p = 0.01). With respect to donors, more than one apheresis was needed in three BIO donors, one of them with PLEX. The use of BIO was the only risk factor for mobilization failure in patients who needed PLEX (hazard ratio 10.3; 95% confidence interval 1.3–77.8). Conclusion The study revealed that BIO had a lower efficacy for stem cell mobilization when the only treatment was G-CSF, especially in poor mobilizers needing PLEX.