Allogeneic hematopoietic stem-cell transplantation for patients with Richter transformation: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.

Management of Richter transformation (RT) is particularly challenging, with survival estimates <1 year. We report on outcomes of 66 RT patients undergoing allogeneic-HCT (allo-HCT) between 2008 and 2018 registered with the EBMT. Median age at allo-HCT was 56.2 years (interquartile range (IQR), 51.3-63.1). Median time from RT to allo-HCT was 6.9 months (IQR, 4.9-11) and 28 (42.4%) were in complete remission (CR). The majority underwent reduced intensity conditioning (66.2%) using peripheral blood derived stem cells. Eighteen (27.3%) patients had a matched sibling donor, 24 (36.4%) a matched unrelated donor and the remaining were mismatched. Median follow-up was 6.6 years; 1- and 3- year overall and progression free survival (PFS) (95% CI) was 65% (54-77) and 39% (27-51) and 53% (41-65) and 29% (18-40), respectively. Patients in CR at time of allo-HCT had significantly better 3-year PFS (39% vs. 21%, p = 0.032). Cumulative incidences of grade II-IV acute graft versus host disease (GVHD) at day +100 was 41% (95% CI 29-53) and chronic GVHD at 3 years was 53% (95% CI 41-65). High rates of non-relapse mortality (NRM) were observed; 38% (95% CI, 26-50) at 3 years. Although potentially curative, approaches to reduce considerable NRM and chronic GVHD rates are required.

Endothelial Activation and Stress Index (EASIX) to predict mortality after allogeneic stem cell transplantation: a prospective study.

BACKGROUND: We previously reported that the "Endothelial Activation and Stress Index" (EASIX; ((creatinine×lactate dehydrogenase)÷thrombocytes)) measured before start of conditioning predicts mortality after allogeneic hematopoietic stem cell transplantation (alloSCT) when used as continuous score. For broad clinical implementation, a prospectively validated EASIX-pre cut-off is needed that defines a high-risk cohort and is easy to use. METHOD: In the current study, we first performed a retrospective cohort analysis in n=2022 alloSCT recipients and identified an optimal cut-off for predicting non-relapse mortality (NRM) as EASIX-pre=3. For cut-off validation, we conducted a multicenter prospective study with inclusion of n=317 first alloSCTs from peripheral blood stem cell in adult patients with acute leukemia, lymphoma or myelodysplastic syndrome/myeloproliferative neoplasms in the European Society for Blood and Marrow Transplantation network. RESULTS: Twenty-three % (n=74) of alloSCT recipients had EASIX-pre ≥3 taken before conditioning. NRM at 2 years was 31.1% in the high EASIX group versus 11.5% in the low EASIX group (p<0.001). Patients with high EASIX-pre also had worse 2 years overall survival (51.6% vs 70.9%; p=0.002). We were able to validate the cut-off and found that EASIX ≥3 was associated with more than twofold increased risk for NRM in multivariate analysis (HR=2.18, 95% CI 1.2 to 3.94; p=0.01). No statistically significant difference could be observed for the incidence of relapse. CONCLUSIONS: The results of this study provide a prospectively validated standard laboratory biomarker index to estimate the transplant-related mortality risk after alloSCT. EASIX ≥3 taken before conditioning identifies a population of alloSCT recipients who have a more than twofold increased risk of treatment-related mortality.

Prophylaxis and management of graft-versus-host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation.

Graft-versus-host disease (GVHD) is a major factor contributing to mortality and morbidity after allogeneic haematopoietic stem-cell transplantation (HSCT). In the last 3 years, there has been regulatory approval of new drugs and considerable change in clinical approaches to prophylaxis and management of GVHD. To standardise treatment approaches, the European Society for Blood and Marrow Transplantation (EBMT) has updated its clinical practice recommendations. We formed a panel of one methodologist and 22 experts in the field of GVHD management. The selection was made on the basis of their role in GVHD management in Europe and their contributions to the field, such as publications, presentations at conferences, and other research. We applied the GRADE process to ten PICO (patient, intervention, comparator, and outcome) questions: evidence was searched for by the panel and graded for each crucial outcome. In two consensus meetings, we discussed the evidence and voted on the wording and strengths of recommendations. Key updates to the recommendations include: (1) primary use of ruxolitinib in steroid-refractory acute GVHD and steroid-refractory chronic GVHD as the new standard of care, (2) use of rabbit anti-T-cell (thymocyte) globulin or post-transplantation cyclophosphamide as standard GVHD prophylaxis in peripheral blood stem-cell transplantations from unrelated donors, and (3) the addition of belumosudil to the available treatment options for steroid-refractory chronic GVHD. The EBMT proposes to use these recommendations as the basis for routine management of GVHD during allogenic HSCT. The current recommendations favour European practice and do not necessarily represent global preferences.

Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis in HLA-Matched and Haploidentical Donor Transplantation for Patients with Hodgkin Lymphoma: A Comparative Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation.

Post-transplantation cyclophosphamide (PTCy) has emerged as a promising approach for preventing graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is a lack of studies examining the impact of this GVHD prophylaxis when different donor types are used in patients with Hodgkin lymphoma (HL). This study compared the outcomes of patients with HL undergoing HSCT from HLA-matched donors, including matched sibling donors (MSDs) and matched unrelated donors (MUDs), and haploidentical donors, using PTCy as the GVHD prophylaxis approach in all cohorts. We retrospectively compared outcomes of allo-HSCT from 166 HLA-matched donors (96 sibling and 70 unrelated donors) and 694 haploidentical donors using PTCy-based GVHD prophylaxis in patients with HL registered in the European Society for Blood and Marrow Transplantation database from 2010 to 2020. Compared to HLA-matched HSCT, haploidentical donor HSCT was associated with a significantly lower rate of platelet engraftment (86% versus 94%; P < .001) and a higher rate of grade II-IV acute GVHD (34% versus 24%; P = .01). The 2-year cumulative incidence of nonrelapse mortality (NRM) was significantly lower in the HLA-matched cohort compared to the haploidentical cohort (10% versus 18%; P = .02), resulting in a higher overall survival (OS) rate (82% versus 70%; P = .002). There were no significant differences between the 2 cohorts in terms of relapse, progression-free survival, or GVHD-free relapse-free survival. In multivariable analysis, haploidentical HSCT was associated with an increased risk of grade II-IV acute GVHD and NRM and worse OS compared to HLA-matched HSCT. Our findings suggest that in the context of PTCy-based GVHD prophylaxis, transplantation from HLA-matched donors appears to be a more favorable option compared to haploidentical HSCT.

A novel agent for myeloma causing toxic keratopathy, belantamab mafodotin: a case report and literature review / Belantamabe-mafodotina, um novo agente para mieloma, causando ceratopatia tóxica: relato de caso e revisão da literatura

ABSTRACT A 60-year-old-male with refractory relapsed multiple myeloma presented with redness, pain, foreign body sensation, and blurred vision in both eyes that gradually increased after his third belantamab mafotodin infusion. Biomicroscopy revealed bilateral microcyst-like epithelial changes and epithelial crystal-like deposits, whereas in vivo confocal microscopy revealed intraepithelial and subepithelial hyperreflective deposits in corneal epithelium. Belantamab mafodotin therapy was discontinued for seven weeks due to corneal toxicity, which cleared progressively. We aim to demonstrate belantamab mafodotin-related corneal toxicity that may be detected using slit lamp and in vivo confocal biomicroscopy.

RESUMO Um homem de 60 anos, diagnosticado com mieloma múltiplo recidivante refratário, apresentou vermelhidão, dor, sensação de corpo estranho e visão turva em ambos os olhos, aumentando gradualmente após sua terceira infusão de belantamabe mafodotina. À biomicroscopia, foram observadas alterações epiteliais bilaterais semelhantes a microcistos e depósitos epiteliais semelhantes a cristais. A microscopia confocal in vivo revelou depósitos hiper-refletivos intraepiteliais e subepiteliais na córnea. Devido à toxicidade corneana, a terapia com belantamabe mafodotina foi interrompida por sete semanas e a toxicidade foi gradualmente resolvida. Nosso objetivo é demonstrar os achados à biomicroscopia confocal in vivo e à lâmpada de fenda da toxicidade corneana relacionada ao belantamabe mafodotina.

Current incidence, severity, and management of veno-occlusive disease/sinusoidal obstruction syndrome in adult allogeneic HSCT recipients: an EBMT Transplant Complications Working Party study.

The current incidence, diagnostic policy, management, and outcome of VOD/SOS at EBMT centers were studied. All centers that had performed allogeneic HSCTs in adult patients within one defined year were invited to the study. Seventy-one centers participated with a total of 2886 allogeneic transplantations and 93 cases of VOD/SOS in 2018. The cumulative incidence of VOD/SOS at day 21 was 1.8% and at day 100 2.4%. Of 67 cases with detailed data, 52 were classical and 15 (22%) late onset (>day 21). According to the EBMT criteria, 65/67 patients had at least two VOD/SOS risk factors. The severity grades were: mild 0, moderate 3, severe 29, very severe 35. Fifty-four patients were treated with defibrotide. VOD/SOS resolved in 58% of the patients, 3/3 with moderate, 22/28 with severe, and 12/33 with very severe grade (p < 0.001). By day 100, 57% of the patients were alive; 3/3 with moderate, 22/29 with severe, and 13/35 with very severe VOD/SOS (p = 0.002). In conclusion, the incidence of VOD/SOS was low. Severe and very severe grades dominated. Very severe grade predicted poor outcome compared to severe grade further supporting the concept of early diagnosis and treatment to avoid a dismal outcome.

Unmet clinical needs and challenges in the management of acute leukemia in Turkey: a modified Delphi study.

Aim: To determine the unmet needs and challenges in management, diagnosis, treatment, follow-up and patient-physician communication in acute leukemia (AL). Materials & methods: The study was based on a modified Delphi approach. A questionnaire including the major potential obstacles was circulated twice among 13 hematologists. Results: The obstacles in AL management were limited access to the novel treatments and genetic tests, limited bed capacity, insufficient level of knowledge among allied health personnel, limited availability of psycho-oncological support and low levels of awareness in the population about the importance of stem cell donation. Conclusion: The challenges in the management of AL are critical to guide the efforts to improve the quality of healthcare delivery and the evidence-based decision making at treatment of AL patients.

Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a refined classification from the European society for blood and marrow transplantation (EBMT).

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life-threatening complication that can develop after hematopoietic cell transplantation (HCT). A new definition for diagnosis, and a severity grading system for SOS/VOD in adult patients, was reported a few years ago on behalf of the European Society for Blood and Marrow Transplantation (EBMT). The aim of this work is to update knowledge regarding diagnosis and severity assessment of SOS/VOD in adult patients, and also its pathophysiology and treatment. In particular, we now propose to refine the previous classification and distinguish probable, clinical and proven SOS/VOD at diagnosis. We also provide an accurate definition of multiorgan dysfunction (MOD) for SOS/VOD severity grading based on Sequential Organ Failure Assessment (SOFA) score.

Impact of measurable residual disease on outcomes of unrelated donor haematopoietic cell transplantation with post-transplant cyclophosphamide in AML in first complete remission.

Pre-transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo-HCT). The impact of MRD on the outcomes of post-transplant cyclophosphamide (PTCy)-based allo-HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD-], n = 165; MRD positive [MRD+], n = 107) with a median follow-up of 19 (range: 16-24) months were studied. The incidence of grades II-IV and grades III-IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2-year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD- cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39-4.72), lower leukaemia-free survival (LFS) (HR = 2.04, 95% CI: 1.23-3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04-3.25) and GVHD-free, relapse-free survival (GRFS) (HR = 1.69, 95% CI: 1.10-2.58). MRD status did not have a significant impact on non-relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo-HCT with PTCy, pre-transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS.

Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT.

In this registry-based study we retrospectively compared outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with acute lymphoblastic leukemia (ALL) following conditioning with total body irradiation (TBI) combined with either cyclophosphamide (Cy) or fludarabine (Flu). TBI 12 Gy + Cy was used in 2105 cases while TBI 12 Gy + Flu was administered to 150 patients in first or second complete remission. In a multivariate model adjusted for other prognostic factors, TBI/Cy conditioning was associated with a reduced risk of relapse (HR = 0.69, p = 0.049) and increased risk of grade 2-4 acute graft-versus-host disease (GVHD, HR = 1.57, p = 0.03) without significant effect on other transplantation outcomes. In a matched-pair analysis the use of TBI/Cy as compared to TBI/Flu was associated with a significantly reduced rate of relapse (18% vs. 30% at 2 years, p = 0.015) without significant effect on non-relapse mortality, GVHD and survival. We conclude that the use of myeloablative TBI/Cy as conditioning prior to allo-HCT for adult patients with ALL in complete remission is associated with lower risk of relapse rate compared to TBI/Flu and therefore should probably be considered a preferable regimen.

Safety and efficacy of autologous stem cell transplantation in dialysis-dependent myeloma patients-The DIADEM study from the chronic malignancies working party of the EBMT.

The role of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) in the treatment of myeloma (MM) patients with severe and/or dialysis-dependent renal impairment remains uncertain. We report on the outcomes of 110 patients (median age 57 years) who had become dialysis-dependent pre-ASCT and who underwent a first ASCT between 1997 and 2017. Sixty-three (57%) patients had light chain MM. All patients required dialysis (94% hemodialysis and 6% peritoneal). Forty-four of 71 (62%) patients received bortezomib-based induction regimens and 42 (39%) patients had achieved at least a very good partial response (VGPR) pre-ASCT. Melphalan dosing was as follows: ≤140 mg/m2 (82%), and >140 mg/m2 (18%). The median PFS after ASCT was 35 months (95% CI: 21.5-42.2) and the median OS 102 months (95% CI: 70.4-129.1). At 1, 2, and 5 years after ASCT, 8% (95% CI 3-14%), 13% (6-20%), and 20% (12-29%) of patients, respectively, had achieved dialysis independence. In multivariate analyses of OS and PFS including age at ASCT, response at ASCT, and year of ASCT, younger age at ASCT and better response at ASCT (CR/VGPR/PR vs. MR/SD/progression) were significantly associated with better OS and PFS.

Fludarabine versus cyclophospamide in combination with myeloablative total body irradiation as conditioning for patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation. A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Total body irradiation (TBI) at a dose of 12 Gy combined with cyclophosphamide (CyTBI12Gy) is one of the standard myeloablative regimens for patients with acute myeloid leukemia (AML) treated with allogeneic hematopoietic cell transplantation (allo-HCT). In clinical practice, cyclophosphamide may be substituted with fludarabine (FluTBI12Gy) to reduce toxicity. We retrospectively compared outcomes of CyTBI12Gy with FluTBI12Gy for patients with AML treated in complete remission (CR) with allo-HCT from either a matched sibling or unrelated donor. Of 1684 adults who met inclusion criteria, 109 patients in each group were included in a matched-pair analysis. The cumulative incidence of relapse at 2 years was 25% in the FluTBI12Gy compared to 28% in the CyTBI12Gy group (p = .44) while non-relapse mortality (NRM) was 17% versus 19%, (p = .89) respectively. The rates of leukemia-free survival and overall survival were 65% versus 54% (p = .28) and 70% versus 60.5% (p = .17). Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) was significantly lower for FluTBI12Gy than CyTBI12Gy (16% vs. 34%, p = .005), while the incidences of grade 3-4 acute GVHD and chronic GVHD did not differ significantly. The probability of GVHD and relapse-free survival was 49% in the FluTBI12Gy and 41% in the CyTBI12Gy group (p = .17). We conclude that for patients with AML treated with allo-HCT in CR, cyclophosphamide may be substituted with fludarabine in a regimen based on TBI at a dose of 12 Gy without negative impact on the efficacy. FluTBI12Gy is associated with reduced risk of grade 2-4 acute GVHD and encouraging survival rates.

Current Practice of Oral Care for Hematopoietic Stem Cell Transplant Patients: A Survey of the Eastern Mediterranean Blood and Marrow Transplantation Group.

INTRODUCTION: The oral cavity is one of the most common sites impacted by hematopoietic stem cell transplantation (HSCT) with acute complications including mucositis, bleeding, salivary gland dysfunction, infection, and taste alteration. These complications may result in significant morbidity and can negatively impact outcomes such as length of stay and overall costs. As such, oral care during HSCT for prevention and management of oral toxicities is a standard component of transplant protocols at all centers. The objective of this study was to evaluate the current oral care practices for patients during HSCT at different transplant centers within the Eastern Mediterranean region. MATERIAL AND METHODS: An internet-based survey was directed to 30 transplant centers in the Eastern Mediterranean region. The survey included five sections asking questions related to (1) transplant center demographics; (2) current oral care protocol used at the center and type of collaboration (if any) with a dental service; (3) use of standardized oral assessment tools and grading systems for mucositis; (4) consultations for management of oral complications; and (5) oral health needs at each center. Data are presented as averages and percentages. RESULTS: A total of 16 responses from 11 countries were collected and analyzed, indicating a response rate of 53%. Eight centers reported that a dentist was part of the HSCT team, with four reporting oral medicine specialists specifically being part of the team. Almost all centers (15/16; 93%) had an affiliated dental service to facilitate pre-HSCT dental clearance with an established dental clearance protocol at 14 centers (87%). Dental extraction was associated with the highest concern for bleeding and the need for platelet transfusion. With respect to infection risk, antibiotic prophylaxis was considered in the setting of low neutrophil counts with restorative dentistry and extraction. All centers provide daily reinforcement of oral hygiene regimen. The most frequently used mouth oral rinses included sodium bicarbonate (68%) and chlorhexidine gluconate (62%), in addition to ice chips for dry mouth (62%). The most frequently used mucositis assessment tools were the World Health Organization scale (7/16; 43%) and visual analogue scale for pain (6/16; 37%). Mucositis pain was managed with lidocaine solution (68.8%), magic mouth wash (68.8%) and/or systemic pain medications (75%). CONCLUSIONS: Scope and implementation of oral care protocols prior to and during HSCT varied between transplant centers. The lack of a universal protocol may contribute to gaps in oral healthcare needs and management for this group of patients. Further dissemination of and education around available oral care guidelines is warranted. CLINICAL RELEVANCE: Considering oral care during HSCT a standard component of transplant protocols, the current study highlights the common oral care practices for patients at centers within the Eastern Mediterranean region.

Reduced 8-Gray Compared to Standard 12-Gray Total Body Irradiation for Allogeneic Transplantation in First Remission Acute Lymphoblastic Leukemia: A Study of the Acute Leukemia Working Party of the EBMT.

In this registry-based study, we compared outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) in adult patients with acute lymphoblastic leukemia (ALL) transplanted in first complete remission (CR-1), following conditioning with total body irradiation (TBI) at a standard 12-Gray or at a lower 8-Gray total dose. Patients received fludarabine (flu) as the sole chemotherapy complementing TBI. Eight-Gray TBI/flu was used in 494 patients and 12-Gray TBI/flu in 145 patients. Eighty-eight (23.1%) and 36 (29%) of the patients had Ph-negative B-ALL, 222 (58.3%) and 53 (42.7%) had Ph-positive B-ALL, 71 (18.6%) and 35 (28.2%) T-ALL, respectively (P = 0.008). Patients treated with 8-Gray were older than ones received 12-Gray (median 55.7 versus 40.3 years, P < 0.0001) and were more frequently administered in vivo T-cell depletion (71% versus 40%, P <0.0001). In a multivariate model adjusted for age, type of ALL, and other prognostic factors, leukemia-free survival (primary endpoint) as well as relapse, nonrelapse mortality, overall survival, and GVHD-free, relapse-free survival were not influenced by the TBI dose. These results were confirmed when we focused on patients <55 years of age (median 47 years). Patients with Ph-positive ALL or T-ALL had significantly better survival outcomes than ones with Ph-negative B-ALL, mainly due to significantly fewer relapses. We conclude that 8-Gray TBI is sufficient for adult patients with ALL transplanted in CR-1 with no additional benefit of augmenting the conditioning intensity to 12-Gray.

Donor lymphocyte infusions after haploidentical stem cell transplantation with PTCY: A study on behalf of the EBMT cellular therapy & immunobiology working party.

Donor lymphocyte infusion (DLI) is a treatment option to prevent or treat relapse after allogeneic hematopoietic cell transplantation (HCT). We here report data for 173 patients who received one or multiple DLIs after haploidentical-HCT with post-transplant cyclophosphamide (PTCY) at 47 EBMT centers from 2009 to 2018. Indication for DLI was: prophylactic for 59 (34.3%), preemptive for 20(11.6%), and therapeutic for 93(54.1%). For the prophylactic group, the median number of DLIs was 1 (IQR:1-2.5) with a median first dose of 0.1 × 106 CD3+ T cell/kg, for the preemptive 2 (IQR:1-3) with 0.5 × 106 CD3+ T cell/kg, for the therapeutic 1 (IQR:1-3) with 1 × 106CD3+ Tcell/kg, respectively. OS after first DLI was 61% (46-75%) for prophylactic, 40% (19-61%) for preemptive, and 22% (13-31%) for therapeutic. CI of II-IV aGVHD and cGVHD was 17% (7-27%) and 53% (40-67%) for the prophylactic, 20% (2-38%) and 21% (3-39%) for the preemptive, 17% (9-24%) and 24% (15-33%) for the therapeutic group, respectively. Our data show great variability in the indications and modalities of DLI across responding EBMT centers. Survival rates remain relatively low in patients with active disease. While the cumulative incidence of aGVHD appears acceptable, we showed a high incidence of cGVHD in the prophylactic group, compared with preemptive and therapeutic DLI. These data should be investigated further in prospective clinical trials.

Total body irradiation plus fludarabine versus busulfan plus fludarabine as a myeloablative conditioning for adults with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation. A study on behalf of the Acute Leukemia Working Party of the EBMT.

Cyclophosphamide is frequently substituted with fludarabine (Flu) in conditioning regimens before allogeneic hematopoietic cell transplantation (allo-HCT). We aimed to compare retrospectively, total body irradiation (12 Gy) plus Flu (FluTBI12) versus busulfan (Bu) plus Flu (FB4) as a myeloablative conditioning before allo-HCT in patients with acute myeloid leukemia (AML). Out of 3203 patients who met the inclusion criteria, 109 patients treated with FluTBI12 and 213 treated with FB4 were included in a final matched-pair analysis. In both groups, median patient age was 41 years, first or second complete remission (CR1/CR2) proportion was 78%/22%, allo-HCT from an unrelated donor was performed in 78% of patients. The probabilities of leukemia-free survival and overall survival at 2 years in FluTBI12 and FB4 groups were 65% vs. 60% (p = 0.64) and 70% vs. 72% (p = 0.87), respectively. The cumulative incidence of relapse was 19% vs. 29% (p = 0.11), while non-relapse mortality was 16% vs. 11%, respectively (p = 0.13). There were no statistical differences in both acute and chronic graft-versus-host disease (GVHD) incidence. The probability of GVHD-free, relapse-free survival (GRFS) was 49% for both groups. FluTBI12 and FB4 are comparable myeloablative regimens before allo-HCT in AML patients transplanted in CR1 and CR2.

A novel agent for myeloma causing toxic keratopathy, belantamab mafodotin: a case report and literature review.

A 60-year-old-male with refractory relapsed multiple myeloma presented with redness, pain, foreign body sensation, and blurred vision in both eyes that gradually increased after his third belantamab mafotodin infusion. Biomicroscopy revealed bilateral microcyst-like epithelial changes and epithelial crystal-like deposits, whereas in vivo confocal microscopy revealed intraepithelial and subepithelial hyperreflective deposits in corneal epithelium. Belantamab mafodotin therapy was discontinued for seven weeks due to corneal toxicity, which cleared progressively. We aim to demonstrate belantamab mafodotin-related corneal toxicity that may be detected using slit lamp and in vivo confocal biomicroscopy.

Haploidentical Versus Matched Sibling Donor Hematopoietic Stem Cell Transplantation for Adult Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia: A Study From the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

The results of haploidentical stem cell transplantation (haploHCT) for patients with acute lymphoblastic leukemia (ALL) transplanted in active disease remain largely unknown. We retrospectively analyzed adult patients with R/R ALL who underwent haploHCT or matched sibling donor (MSD-HCT) as a first transplantation between 2012 and 2020. The analysis comprised 274 patients, 94 had a haploHCT, and 180 had an MSD-HCT. The median follow-up was 32 months. The median age was 33 (range 18-76) and 37 (18-76) years in the haplo- and MSD-HCT groups, respectively. Post-transplant cyclophosphamide (PTCy) was used in 88% of haploHCT and in 4% of the MSD-HCT group. Graft-versus-host disease grade III-IV was higher in haploHCT than in the MSD-HCT group (18% versus 9%; P = 0.042). The 2-year chronic (c) graft-versus-host disease rates were 17% versus 33% (hazard ratio [HR] = 0.56; P = 0.14), respectively. By multivariate analysis, relapse incidence, and leukemia-free survival were not significatively different between the transplant groups, while nonrelapse mortality (NRM) was significantly higher (25% versus 18% at 2 years; HR = 2.03; P = 0.042) and overall survival (OS) lower (22% versus 38% at 2 years; HR = 1.72; P = 0.009) in the haploHCT group compared with the MSD-HCT group. We conclude that the 2-year OS of R/R ALL patients undergoing MSD transplants is significantly better than in haploHCT with a higher NRM in the latter.

Posttransplant cyclophosphamide-based anti-graft-vs-host disease prophylaxis in patients with acute lymphoblastic leukemia treated in complete remission with allogeneic hematopoietic cell transplantation from human leukocyte antigen-mismatched unrelated donors versus haploidentical donors: A study on behalf of the ALWP of the EBMT.

BACKGROUND: Both mismatched unrelated donor (MMUD) and haploidentical (haplo) transplantation are valid options in patients with high-risk acute lymphoblastic leukemia (ALL) lacking a matched donor. METHODS: The study compared the outcomes of adult patients with ALL in complete remission (CR) who underwent 9/10 MMUD versus haplo transplantation with posttransplant cyclophosphamide (PTCy) as graft-vs-host disease (GVHD) prophylaxis in 2010-2020. RESULTS: The study included 781 patients (MMUD, 103; haplo, 678). The median age was 40 (19-73) and 38 (18-75) years, respectively (p = .51). The most frequent immunosuppression agents added to PTCy were mycophenolate mofetil (MMF)/cyclosporine A and MMF/tacrolimus. In vivo T-cell depletion (anti-thymocyte globulin) was administered to 21% and 8% of the transplants, respectively (p < .0001). Neutrophil (absolute neutrophil count >0.5 × 109 /L) recovery was achieved in 97.1% versus 96.7% versus (p = 1) in MMUD and haplo, respectively. Nonrelapse mortality and relapse incidence were not significantly different between MMUD and haplo, hazard ratio (HR) = 1.45 (95% confidence interval [CI], 0.81-2.62; p = .21) and HR = 0.81 (95% CI, 0.52-1.28, p = .38), respectively. HRs for leukemia-free survival, overall survival, and GVHD-free, relapse-free survival were respectively, HR = 1.05 (95% CI, 0.73-1.50, p = .8), HR = 1.17 (95% CI, 0.77-1.76, p = .46), and HR = 1.07 (95% CI, 0.78-1.46, p = .7) for haplo compared to MMUD. Acute (a)GVHD grade 2-4 was significantly higher with haplo, HR = 1.73 (95% CI, 1.08-2.76, p = .023), whereas aGVHD grade 3-4 and chronic GVHD did not differ significantly between the two transplant groups. CONCLUSION: Outcomes of MMUD and haplo transplants with PTCy-based GVHD prophylaxis for ALL patients in CR are similar, apart from a higher incidence of aGVHD with haplo transplants.