Gunhan Gurman

AlloHCT remains a curative option for R/R Hodgkin lymphoma despite advances with BV and CPIs. This study evaluates its role and outcomes in this challenging patient population. This retrospective oligocentric analysis involved 70 patients with R/R classical HL who underwent alloHCT. Patients were split into two treatment cohorts: era1 (2004-2010), 16 patients, and era2 (2011-2021), 54 patients. Among the cohort, sixty-three patients had previously received an autologous stem cell transplant. Forty patients were administered only (n=29) BV or BV preceding CPI (n=11) before alloHCT. A median follow-up of 64 months (40.7-87.3) revealed a 100-day non-relapse mortality (NRM) rate of 26%, with the 3-year overall survival (OS) and progression-free survival (PFS) reported as 39% and 28%, respectively. AlloHCT using haplotype-matched donors was linked to better OS and PFS. Post-transplant cyclophosphamide (post-tx CY) as a prophylactic approach for graft versus host disease (GVHD) significantly improved OS and PFS. A complete response (CR) during the post-transplant phase significantly improved OS and PFS. Indeed, better OS, PFS, and a reduced rate of NRM were observed in the pre/post-alloHCT BV and CPI group, although we could not demonstrate statistical significance. The survival (OS, PFS) curves and NRM rates were similar for both eras. AlloHCT is a potentially practical therapeutic approach in responding to R/R HL patients.

This chapter introduces the increasing significance of mesenchymal stromal/stem cell (MSC) production in regenerative medicine and cellular therapeutics, outlines the growing interest in MSCs for various medical applications, and highlights their potential in advanced therapy medicinal products (ATMPs) and the advancements in cell culture technologies that have facilitated large-scale MSC production under Good Manufacturing Practices (GMP), ensuring safety and efficacy. This chapter describes an optimized upstream protocol for laboratory-scale MSC production from different tissue sources. This protocol, conducted in flasks, controls critical parameters and lays the foundation for downstream processing to generate ATMPs. This comprehensive approach underscores the potential of MSCs in clinical applications and the importance of tailored production processes.

Allogeneic hematopoietic stem cell transplantation is a well-established approach for patients diagnosed with primary myelofibrosis and remains the only potentially curative treatment. To present the overall outcome of patients with myelofibrosis treated with allogeneic hematopoietic stem cell transplantation. A retrospective cross-sectional study. This study is a retrospective analysis of 26 consecutive patients with primary myelofibrosis who underwent transplantation at our center between January 2002 and January 2022. Disease and transplant variables contributing to outcomes were analyzed. The median age at the time of transplantation was 52.5 (range, 32-63) years and the median time from diagnosis to allogeneic hematopoietic stem cell transplantation was 25 (range, 3.1-156.8) months. Myeloablative conditioning and reduced-intensity conditioning regimens were used in 8 (30.8%) and 18 (69.2%) transplantations, respectively. Neutrophil and platelet engraftment was achieved in 23 patients at a median follow-up of 21.2 months (range, 12 days to 234.8 months). Primary graft failure occurred in 1 of 23 patients (4.3%). Neutrophil and platelet engraftment occurred at a median of 16 (range, 12-39) days and 20 (range, 11-78) days, respectively. Acute graft-versus-host disease was seen in 11 of 22 patients engrafted allografts, of which 7 (31.8%) were grade 3-4 acute graft-versus-host disease. Eight patients (36.4%) developed chronic graft-versus-host disease, and three cases were extensive. Four patients (19%) relapsed after a median of 5.5 months, and three patients received donor lymphocyte infusion. The 3-year overall survival rate of the entire study population was 46.2%. The median overall survival was not reached in the myeloablative conditioning group; however, it was 11.9 months in the reduced-intensity conditioning group (p =0.3). According to the donor graft source, the median overall survival was 0.73 months in mismatched unrelated graft recipients, 12 months in matched sibling donors, and not reached in matched unrelated graft recipients (p = 0.03). The 3-year progression-free survival rate of patients who survived > 100 days was 74.7%. The effect of JAK-2 status, graft source, conditioning regimen or dynamic international prognostic scoring system on progression-free survival was not statistically significant. Given the poor prognosis of non-transplant recipients and the lack of non-transplant curative approaches, our results support the consideration of allogeneic hematopoietic stem cell transplantation for eligible patients with primary myelofibrosis.

Eltrombopag has an off-label indication for haematopoietic cell transplantation in patients experiencing delayed thrombocyte recovery and/or thrombocytopaenia. To present our centre’s experience of using this agent not only for post- haematopoietic cell transplantation thrombocytopaenia but also for poor graft functioning in the post-haematopoietic cell transplantation setting. Retrospective cross-sectional study. Thirty-nine patients who had persistent cytopaenia following haematopoietic cell transplantation and treated with eltrombopag at our centre between October 2011 and December 2021 were retrospectively identified. During this period, 9 (23.1%) and 30 (76.9%) patients who underwent allogeneic transplantations, respectively, received eltrombopag. The female-to-male ratio was 12:27, and the median transplant age was 49 (18-70) years. Eight (20.5%) patients had isolated thrombocytopaenia, 19 (49.4%) had bi-lineage cytopaenia and 12 (30.1%) had pancytopaenia. Patients received a median of 50 mg/day (25-150 mg/day) of eltrombopagfor a median duration of 82 (24-386) days. Nine (23.1%) patients had autologous haematopoietic cell transplantation, and 30 (76.9%) had allogeneic haematopoietic cell transplantation (14 unrelated, 9 sibling and 7 haploidentical). The median donor age was 32 (20-67) years. The median follow-up was 16.4 (1.8-84.3) months. The median pre-treatment platelet count was 11x10⁹/l (1-23), which increased to 41x10⁹/l (6-150). The median platelet count increment was 29.5x10⁹/l (p = 0.001). The pre-treatment median neutrophil count was 1.19x10⁹/l (0.39-5.1), which increased to 2.35 x10⁹/l (0.1-5.33) (p = 0.05), and the pre-treatment median haemoglobin was 8.3 (6.2-14) g/dl, which increased to 10 (6.2-14) g/dl (p = 0.001) with eltrombopag. No eltrombopag-related hepatotoxicity occurred; however, 1 (2.6%) patient failed to continue treatment because of two consecutive episodes of deep venous thrombosis. Six (15.4%) patients were unresponsive to eltrombopag and dependent on blood product transfusions. After a median time of 82 days, 61.5% of the patients discontinued eltrombopag successfully. The results confirmed that eltrombopag could provide a rapid, sustained response in patients with poor graft functioning after haematopoietic cell transplantation. This finding is essential given the high rate of non-relapse mortality caused by poor graft functioning after haematopoietic cell transplantation.

Objective: Patients with solid malignancies are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection than the healthy population. The outcome of SARS-CoV-2 infection in highly immunosuppressed populations, such as in patients with hematological malignancies, is a point of interest. We aimed to analyze the symptoms, complications, intensive care unit admissions, and mortality rates of patients with hematological malignancies infected with SARS-CoV-2 in Turkey. Materials and Methods: In this multicenter study, we included 340 adult and pediatric patients diagnosed with SARS-CoV-2 from March to November 2020. Diagnosis and status of primary disease, treatment schedules for hematological malignancies, time from last treatment, life expectancy related to the hematological disease, and comorbidities were recorded, together with data regarding symptoms, treatment, and outcome of SARS-CoV-2 infection. Results: Forty four patients were asymptomatic at diagnosis of SARSCoV-2 infection. Among symptomatic patients, fever, cough, and dyspnea were observed in 62.6%, 48.8%, and 41.8%, respectively. Sixtynine (20%) patients had mild SARS-CoV-2 disease, whereas moderate, severe, and critical disease was reported in 101 (29%), 71 (20%), and 55 (16%) patients, respectively. Of the entire cohort, 251 (73.8%) patients were hospitalized for SARS-CoV-2. Mortality related to SARS-CoV-2 infection was 26.5% in the entire cohort; this comprised 4.4% of those patients with mild disease, 12.4% of those with moderate disease, and 83% of those with severe or critical disease. Active hematological disease, lower life expectancy related to primary hematological disease, neutropenia at diagnosis of SARS-CoV-2, ICU admission, and first-line therapy used for coronavirus disease-2019 treatment were found to be related to higher mortality rates. Treatments with hydroxychloroquine alone or in combination with azithromycin were associated with a higher rate of mortality in comparison to favipiravir use. Conclusion: Patients with hematological malignancy infected with SARS-CoV-2 have an increased risk of severe disease and mortality.

Objective: The optimal timing of measurable residual disease (MRD) evaluation in acute myeloid leukemia (AML) patients has not been well defined yet. We aimed to investigate the impact of MRD in pre- and post-allogeneic hematopoietic stem cell transplantation (AHSCT) periods on prognostic parameters. Materials and Methods: Seventy-seven AML patients who underwent AHSCT in complete morphological remission were included. MRD analyses were performed by 10-color MFC and 10(-4) was defined as positive. Relapse risk and survival outcomes were assessed based on pre- and post-AHSCT MRD positivity. Results: The median age of the patients was 46 (range: 18-71) years, and 41 (53.2%) were male while 36 (46.8%) were female. The median follow-up after AHSCT was 12.2 months (range: 0.2-73.0). The 2-year overall survival (OS) in the entire cohort was 37.0%, with a significant difference between patients who were MRD-negative and MRD-positive before AHSCT, estimated as 63.0% versus 16.0%, respectively (p=0.005). MRD positivity at +28 days after AHSCT was also associated with significantly inferior 2-year OS when compared to MRD negativity (p=0.03). The risk of relapse at 1 year was 2.4 times higher (95% confidence interval: 1.1-5.6; p=0.04) in the pre-AHSCT MRD-positive group when compared to the MRD-negative group regardless of other transplant-related factors, including pre-AHSCT disease status (i.e., complete remission 1 and 2). Event-free survival (EFS) was significantly shorter in patients who were pre-AHSCT MRD-positive (p=0.016). Post-AHSCT MRD positivity was also related to an increased relapse risk. OS and EFS were significantly inferior among MRD-positive patients at +28 days after AHSCT (p=0.03 and p=0.019). Conclusion: Our results indicate the importance of MRD before and after AHSCT independently of other factors