Search

The advent of novel agents for multiple myeloma (MM) is cause for a re-examination of the incidence of second primary malignancies (SPM5). We examined the SPM rate in MM patients who were enrolled in the prospective observational CALM (Collaboration to Collect Autologous Transplant outcome in Lymphoma and Myeloma) study. Between 2008 and 2012, 3204 patients with MM underwent a first autologous hematopoietic stem cell transplantation. Plerixafor was used as a mobilizing agent for patients with poor (or potentially poor) stem cell mobilization as defined by the respective centers. A total of 135 patients developed SPM5, with a cumulative incidence of 5.3% (95% confidence interval, 4.4 to 6.3) at 72 months. Ninety-four patients developed solid tumors, 30 developed hematologic malignancies, and 11 developed an SPM of an unknown type. The cumulative incidence of known hematologic and solid malignancies were 1.4% and 3.6%, respectively, at 72 months. In a univariate analysis, use of radiotherapy, type of induction regimen, hematopoietic stem cell dose, poor mobilizer status, plerixafor use, and sex did not influence the cumulative incidence of SPMs. Only age over 65 years was statistically associated with an increased incidence. Overall, the incidence of SPMs was comparable to earlier estimations of SPMs in MM. (C) 2018 American Society for Blood and Marrow Transplantation.

Recently, an increasing number of patients with acute lymphoblastic leukemia with a poor Karnofsky Performance Status (KPS) score are considered for allogeneic hematopoietic stem cell transplantation (allo-HCT). Nevertheless, there is paucity of available data about outcome of this fragile population. We report here the results of a retrospective study designed to evaluate outcome of ALL patients undergoing allo-HCT with KPS score ≤80%. The analysis included ALL patients aged ≥18 years, undergoing allo-HCT in first remission between 2000 and 2018, with a KPS score of 50% to 80% at the time of transplant. A total of 1,010 patients were identified. Median age at transplant was 43 years (18-76 years). Median year of transplant was 2011. The KPS score was =80% in 83% of the patients and On multivariate analysis, transplant from 10/10 UD was associated with higher incidence of aGVHD (HR 1.8, p In conclusion, allo-HCT is feasible in patients with acute lymphoblastic leukemia in first remission and KPS score ≤80%, with acceptable NRM and survival rates. Transplant from a MSD was associated with reduced risk of NRM and aGVHD as compared to 10/10 UD. Interestingly, despite the poor KPS score of the patients included in the analysis, a MAC protocol was associated with similar NRM, lower relapse and better LFS and GRFS as compared to RIC in the selected population. Finally, administration of ATG was associated with reduced acute and chronic GVHD rates.

Background Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HSCT). Previous studies have shown that anti- thymocyte globulin (ATG) reduce the incidence of acute and or chronic GVHD after reduced intensity and chemotherapy based myeloablative conditioning regimen pre-HSCT. The impact of the use of ATG following TBI based myeloablative conditioning regimen has been poorly explored. Recent prospective, double-blind phase III study of ATG vs placebo in patients (pts) with MDS or AML following myeloablative conditioning report inferior progression-free survival (PFS) and overall survival (OS) in the ATG arm, especially in the TBI cohort. However, this study includes only small and quite heterogeneous sub-populations within the TBI group. We therefore assessed the effect of ATG in a large homogenous cohort of AML pts undergoing HSCT with TBI and reported to the ALWP of the EBMT. Methods The study included 724 AML pts that underwent HSCT during the years 2008-2016 from a matched sibling (n=412) or 9-10 unrelated donor (n=312), following TBI (>8Gy) based conditioning regimen. All disease statuses were included (CR1=489, CR2=148; refractor=87). Graft source was PB in the majority of pts (n=579, 80%). 251 pts received ATG while 473 did not. Median follow up was 58.8 (28-83) months. The disease and transplant characteristics were similar in both groups except for type of donors, unrelated donor HSCT received ATG in 89% vs 19% in sibling donor HSCT (p Results In univariate analysis, day 100 incidence of acute GVHD II-IV and III-VI was 24.1% vs 33% (p Conclusions The addition of ATG to TBI based conditioning regimen followed by HSCT for AML results in significant reduction of acute and chronic GVHD, translating into a significant reduction in TRM without increasing relapse rate, and a similar LFS or OS.

Assessment of measurable residual disease (MRD) is rapidly transforming the therapeutic and prognostic landscape of a wide range of hematological malignancies. Its prognostic value in acute lymphoblastic leukemia (ALL) has been established and MRD measured at the end of induction is increasingly used to guide further therapy. Although MRD detectable immediately before allogeneic hematopoietic cell transplantation (HCT) is known to be associated with poor outcomes, it is unclear if or to what extent this differs with different types of conditioning. Therefore, in this retrospective multicenter study we explored if MRD detectable before allogeneic HCT for ALL is associated with different outcomes in recipients of myeloablative TBI-based versus chemotherapy-based conditioning. We analyzed outcomes of 2780 patients (median age 38 years, range 18-72) who underwent first HCT in complete remission between 2000 and 2017 using sibling or unrelated 9/10 or 10/10 matched donors. In 1816 of these patients no disease was detectable before transplantation and in 964 patients MRD was detectable (MRD positivity). Conditioning was TBI-based in 2122 (76%) transplants. In the whole cohort MRD positivity was a significant independent factor for lower overall survival (OS) and leukemia-free survival (LFS), and for higher relapse incidence (RI), with respective hazard ratios (HR, 95% confidence intervals) of 1.19 (1.02-1.39), 1.26 (1.1-1.44), 1.51 (1.26-1.8). TBI was associated with a better OS, LFS and RI with HR of 0.75 (0.62-0.90), 0.70 (0.60-0.82) and 0.60 (0.49-0.74), respectively. No significant interaction was found between MRD status and conditioning. When investigating the impact of MRD separately in the TBI and chemotherapy-based conditioning cohorts by multivariate analysis, we found MRD positivity to be associated with lower OS (HR 1.26, 1.05-1.51) and LFS (HR 1.3,1.1-1.53), and higher RI (HR 1.53, 1.23-1.9) in the TBI group, and with higher RI (HR 1.58, 1.13-2.21) in the chemotherapy group. There was no significant association between MRD and other outcomes in this last cohort. TBI based conditioning was associated with improved OS, LFS, and RI in both MRD negative and MRD positive patients (figure). In this large study we confirmed that patients who are MRD negative prior to HCT achieve superior outcomes. This is particularly apparent if TBI conditioning is used. All patients with ALL irrespective of MRD status benefit from TBI based conditioning in myeloablative setting.

Background Allogeneic hematopoietic stem cell transplantation (HCT) remains a challenge in elderly and comorbid AML and MDS patients. This patient population is at increased risk for non-relapse mortality (NRM) when treated with standard myeloablative conditioning and was selected to compare a newly developed treosulfan-based with a well-established reduced intensity busulfan-based preparative regimen in a prospective randomized clinical phase III trial. Methods Adult patients with AML in remission or MDS scheduled for HCT from matched related or unrelated donors, aged ≥50 years or with a comorbidity index (HCT-CI) of >2 were enrolled by a central stratified randomization procedure. Treatment arms consisted of intravenous (IV) treosulfan (10 g/m²/day [d-4 to d-2]) or IV busulfan (3.2 mg/kg/day [d-4 to d-3]), both combined with IV fludarabine (30 mg/m²/day [d-6 to d-2]). The primary objective was to compare event-free survival (EFS) at two years with relapse/progression of disease, graft failure, or death reported as events. Secondary endpoints were safety evaluation (according to CTCAE v4.03), engraftment, chimerism, overall survival (OS), relapse/progression incidence (RI), NRM and acute or chronic GvHD. After a previously conducted confirmatory interim analysis (based on 476 patients), which resulted in early termination of patient accrual due to significant non-inferiority of treosulfan treatment with improved EFS, NRM and OS (Beelen et al., ASH 2017), results of the final analysis of all 570 randomized patients including post surveillance data are provided here. Results Median age of the 551 patients (352 AML; 199 MDS) included in the full analysis set (268 treosulfan; 283 busulfan) was 60 years (range: 31, 70). Frequencies of early adverse events (d-6 to d+28) and incidences of acute and chronic GvHD were largely comparable between the two regimens, while extensive chronic GvHD was numerically in favor of treosulfan (19.7% vs. 26.7%; p=0.0750). Primary neutrophil recovery at day +28 was comparable, while the rate of complete donor-type chimerism (day +28) was higher after treosulfan (93.2% vs. 83.3%; p Conclusions Final evaluation of this phase III trial substantiates the previous confirmatory analysis resulting in significantly improved survival after treosulfan-based conditioning. Due to the reduction of NRM a major clinical benefit of the new treosulfan conditioning regimen was demonstrated in the selected AML/MDS patient population.