Gemtuzumab ozogamicin plus midostaurin in combination with standard '7 + 3' induction therapy in newly diagnosed AML: Results from the SAL-MODULE phase I study.

We conducted a phase I trial in newly diagnosed acute myeloid leukaemia (AML) to investigate the combination of two novel targeted agents, gemtuzumab ozogamicin (GO) and midostaurin, with intensive chemotherapy in FLT3-mutated AML and CBF leukaemia. Three dose levels of midostaurin and one to three sequential doses of 3 mg/m2 GO in combination with '7 + 3' induction were evaluated. Based on safety findings in 12 patients, our results show that 3 mg/m2 GO on Days 1 + 4 and 100 mg midostaurin on Days 8-21 can be safely combined with IC in newly diagnosed AML.

Time from diagnosis to treatment has no impact on survival in newly diagnosed acute myeloid leukemia treated with venetoclax-based regimens.

In newly diagnosed acute myeloid leukemia, immediate initiation of treatment is standard of care. However, deferral of antileukemic therapy may be indicated to assess comorbidities or pre-therapeutic risk factors. We explored the impact of time from diagnosis to treatment on outcomes in newly diagnosed acute myeloid leukemia undergoing venetoclax-based therapy in two distinct cohorts. By querying the Study Alliance Leukemia database and the global health network TriNetX, we identified 138 and 717 patients respectively with an average age of 76 and 72 years who received venetoclax-based firstline therapy. When comparing patients who started treatment earlier or later than 10 days after initial diagnosis, no significant difference in median overall survival was observed - neither in the SAL cohort (7.7 vs. 9.6 months, p=.42) nor in the TriNetX cohort (7.5 vs. 7.2 months, p=.41). Similarly, severe infections, bleeding, and thromboembolic events were equally observed between early and later treatments, both in the overall patient groups and specific subgroups (age ≥75 years or leukocytes ≥20x109/L). This retrospective analysis indicates that delaying the start of venetoclax-based therapy in newly diagnosed acute myeloid leukemia might be a safe option for selected patients, provided that close clinical monitoring is performed.

Remission induction versus immediate allogeneic haematopoietic stem cell transplantation for patients with relapsed or poor responsive acute myeloid leukaemia (ASAP): a randomised, open-label, phase 3, non-inferiority trial.

BACKGROUND: Whether high-dose cytarabine-based salvage chemotherapy, administered to induce complete remission in patients with poor responsive or relapsed acute myeloid leukaemia scheduled for allogeneic haematopoietic stem-cell transplantation (HSCT) after intensive conditioning confers a survival advantage, is unclear. METHODS: To test salvage chemotherapy before allogeneic HSCT, patients aged between 18 and 75 years with non-favourable-risk acute myeloid leukaemia not in complete remission after first induction or untreated first relapse were randomly assigned 1:1 to remission induction with high-dose cytarabine (3 g/m2 intravenously, 1 g/m2 intravenously for patients >60 years or with a substantial comorbidity) twice daily on days 1-3 plus mitoxantrone (10 mg/m2 intravenously) on days 3-5 or immediate allogeneic HSCT for the disease control group. Block randomisation with variable block lengths was used and patients were stratified by age, acute myeloid leukaemia risk, and disease status. The study was open label. The primary endpoint was treatment success, defined as complete remission on day 56 after allogeneic HSCT, with the aim to show non-inferiority for disease control compared with remission induction with a non-inferiority-margin of 5% and one-sided type 1 error of 2·5%. The primary endpoint was analysed in both the intention-to-treat (ITT) population and in the per-protocol population. The trial is completed and was registered at ClinicalTrials.gov, NCT02461537. FINDINGS: 281 patients were enrolled between Sept 17, 2015, and Jan 12, 2022. Of 140 patients randomly assigned to disease control, 135 (96%) proceeded to allogeneic HSCT, 97 (69%) after watchful waiting only. Of 141 patients randomly assigned to remission induction, 134 (95%) received salvage chemotherapy and 128 (91%) patients subsequently proceeded to allogeneic HSCT. In the ITT population, treatment success was observed in 116 (83%) of 140 patients in the disease control group versus 112 (79%) of 141 patients with remission induction (test for non-inferiority, p=0·036). Among per-protocol treated patients, treatment success was observed in 116 (84%) of 138 patients with disease control versus 109 (81%) of 134 patients in the remission induction group (test for non-inferiority, p=0·047). The difference in treatment success between disease control and remission induction was estimated as 3·4% (95% CI -5·8 to 12·6) for the ITT population and 2·7% (-6·3 to 11·8) for the per-protocol population. Fewer patients with disease control compared with remission induction had non-haematological adverse events grade 3 or worse (30 [21%] of 140 patients vs 86 [61%] of 141 patients, χ2 test p<0·0001). Between randomisation and the start of conditioning, with disease control two patients died from progressive acute myeloid leukaemia and zero from treatment-related complications, and with remission induction two patients died from progressive acute myeloid leukaemia and two from treatment-related complications. Between randomisation and allogeneic HSCT, patients with disease control spent a median of 27 days less in hospital than those with remission induction, ie, the median time in hospital was 15 days (range 7-64) versus 42 days (27-121, U test p<0·0001), respectively. INTERPRETATION: Non-inferiority of disease control could not be shown at the 2·5% significance level. The rate of treatment success was also not statistically better for patients with remission induction. Watchful waiting and immediate transplantation could be an alternative for fit patients with poor response or relapsed acute myeloid leukaemia who have a stem cell donor available. More randomised controlled intention-to-transplant trials are needed to define the optimal treatment before transplantation for patients with active acute myeloid leukaemia. FUNDING: DKMS and the Gert and Susanna Mayer Stiftung Foundation.

Mimicking clinical trials with synthetic acute myeloid leukemia patients using generative artificial intelligence.

Clinical research relies on high-quality patient data, however, obtaining big data sets is costly and access to existing data is often hindered by privacy and regulatory concerns. Synthetic data generation holds the promise of effectively bypassing these boundaries allowing for simplified data accessibility and the prospect of synthetic control cohorts. We employed two different methodologies of generative artificial intelligence - CTAB-GAN+ and normalizing flows (NFlow) - to synthesize patient data derived from 1606 patients with acute myeloid leukemia, a heterogeneous hematological malignancy, that were treated within four multicenter clinical trials. Both generative models accurately captured distributions of demographic, laboratory, molecular and cytogenetic variables, as well as patient outcomes yielding high performance scores regarding fidelity and usability of both synthetic cohorts (n = 1606 each). Survival analysis demonstrated close resemblance of survival curves between original and synthetic cohorts. Inter-variable relationships were preserved in univariable outcome analysis enabling explorative analysis in our synthetic data. Additionally, training sample privacy is safeguarded mitigating possible patient re-identification, which we quantified using Hamming distances. We provide not only a proof-of-concept for synthetic data generation in multimodal clinical data for rare diseases, but also full public access to synthetic data sets to foster further research.

Allogeneic hematopoietic cell transplantation for older patients with AML with active disease. A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT).

Older adults with acute myeloid leukemia (AML) refractory to initial or reinduction chemotherapy have a dismal prognosis if they do not undergo hematopoietic stem-cell transplantation (HCT). However, data assessing HCT outcomes from different donors are scarce. We evaluated results from a retrospective analysis on patients aged ≥70 years, with AML not in remission who received an allogeneic HCT from HLA-matched sibling donor (MSD), HLA-10/10 matched unrelated donor (MUD), or T-cell replete haploidentical (Haplo) donor, from 2010 to 2021, reported to the ALWP-EBMT database. A total of 360 patients (median age 72 years, range 70-79) were included in the analysis. Median follow-up for the entire population was 35.5 months. Donors were MSD (n = 58), 10/10 HLA-MUD (n = 228), and Haplo (n = 74). A total of 213 (59.2%) patients were primary induction failures, while 147 (40.8%) were in first or subsequent relapse. Graft source was peripheral blood in 92% of the patients. Patients transplanted from Haplo donors more frequently received marrow grafts (p < 0.01) and presented the combination female donor to male recipient (p < 0.01). The overall 2-year rates of overall survival (OS) and leukemia-free survival (LFS) were: 62.4% (95% CI 47.2-74.3) and 47.6% (95% CI 33.1-60.8) for MSD, 43% (95% CI 35.8-49.9), and 37.5% (95% CI 30.7-44.4) for MUD, and 25.9% (95% CI 15.8-37.2), and 26.5% (95% CI 16.3-37.8) for recipients of Haplo transplants. The 2-year cumulative incidence of relapse (RI) was slightly lower for Haplo recipients at 29.6% (95% CI 19-40.9), for MUD it was 30.2% (95% CI 23.9-36.7), and for MSD 34.9% (95% CI 22-48.2); counterbalanced by a higher incidence of non-relapse mortality (NRM) of 43.9% (95% CI 31.6-55.6) for Haplo recipients, 32.2% (95% CI 26-33.1) for MUD and 17.5% (95% CI 8.4-29.3) for MSD. Graft-versus-host disease (GVHD-free, relapse-free survival (GRFS) was 35.3% (95% CI 22.3-48.5) for MSD, 29.6% (95% CI 23.2-36.2) for MUD, and 19.2% (95% CI 10.7-29.6) for Haplo patients. In the multivariate model, compared to the referent group of MSD recipients, the risk of NRM was higher among patients transplanted from Haplo donors ([hazard ratio] HR 5.1, 95% CI 2.23-11.61, p < 0.001) and MUD (HR 3.21, 95% CI 1.48-0.6.94, p = 0.003). Furthermore, both Haplo and MUD were associated with inferior OS, (HR 3.6, 95% CI 1.98-0.6.56, p < 0.001, and HR 2.3, 95% CI 1.37-0.3.88, p = 0.002, respectively), and LFS (HR 2.24, 95% CI 1.31-0.3.84, p = 0.003, and HR 1.64, 95% CI 1.04-0.2.60, p = 0.034, respectively). Patients transplanted from Haplo donors were also associated with worse GFRS (HR 1.72, 95% CI 1.07-2.77, p:0.025) compared with MSD patients. Older adult AML patients with active disease transplanted from MSD experienced prolonged OS and LFS compared to 10/10 MUD and Haplo due to lower NRM. Prospective clinical trials are warranted.

Precision Culture Scaling to Establish High-Throughput Vasculogenesis Models.

Hydrogel-based 3D cell cultures can recapitulate (patho)physiological phenomena ex vivo. However, due to their complex multifactorial regulation, adapting these tissue and disease models for high-throughput screening workflows remains challenging. In this study, a new precision culture scaling (PCS-X) methodology combines statistical techniques (design of experiment and multiple linear regression) with automated, parallelized experiments and analyses to customize hydrogel-based vasculogenesis cultures using human umbilical vein endothelial cells and retinal microvascular endothelial cells. Variations of cell density, growth factor supplementation, and media composition are systematically explored to induce vasculogenesis in endothelial mono- and cocultures with mesenchymal stromal cells or retinal microvascular pericytes in 384-well plate formats. The developed cultures are shown to respond to vasculogenesis inhibitors in a compound- and dose-dependent manner, demonstrating the scope and power of PCS-X in creating parallelized tissue and disease models for drug discovery and individualized therapies.

CD38 promotes hematopoietic stem cell dormancy.

A subpopulation of deeply quiescent, so-called dormant hematopoietic stem cells (dHSCs) resides at the top of the hematopoietic hierarchy and serves as a reserve pool for HSCs. The state of dormancy protects the HSC pool from exhaustion throughout life; however, excessive dormancy may prevent an efficient response to hematological stresses. Despite the significance of dHSCs, the mechanisms maintaining their dormancy remain elusive. Here, we identify CD38 as a novel and broadly applicable surface marker for the enrichment of murine dHSCs. We demonstrate that cyclic adenosine diphosphate ribose (cADPR), the product of CD38 cyclase activity, regulates the expression of the transcription factor c-Fos by increasing the release of Ca2+ from the endoplasmic reticulum (ER). Subsequently, we uncover that c-Fos induces the expression of the cell cycle inhibitor p57Kip2 to drive HSC dormancy. Moreover, we found that CD38 ecto-enzymatic activity at the neighboring CD38-positive cells can promote human HSC quiescence. Together, CD38/cADPR/Ca2+/c-Fos/p57Kip2 axis maintains HSC dormancy. Pharmacological manipulations of this pathway can provide new strategies to improve the success of stem cell transplantation and blood regeneration after injury or disease.

ETV6::ACSL6 translocation-driven super-enhancer activation leads to eosinophilia in acute lymphoblastic leukemia through IL-3 overexpression.

ETV6::ACSL6 represents a rare genetic aberration in hematopoietic neoplasms and is often associated with severe eosinophilia, which confers an unfavorable prognosis requiring additional anti-inflammatory treatment. However, since the translocation is unlikely to produce a fusion protein, the mechanism of ETV6::ACSL6 action remains unclear. Here, we performed multi-omics analyses of primary leukemia cells and patient-derived xenografts from an acute lymphoblastic leukemia (ALL) patient with ETV6::ACSL6 translocation. We identified a super-enhancer located within the ETV6 gene locus and revealed translocation and activation of the super-enhancer associated with the ETV6::ACSL6 fusion. The translocated super-enhancer exhibited intense interactions with genomic regions adjacent to and distal from the breakpoint at chromosomes 5 and 12, including genes coding inflammatory factors such as IL-3. This led to modulations in DNA methylation, histone modifications, and chromatin structures, triggering transcription of inflammatory factors leading to eosinophilia. Furthermore, the bromodomain and extraterminal domain (BET) inhibitor synergized with standard-of-care drugs for ALL, effectively reducing IL-3 expression and inhibiting ETV6::ACSL6 ALL growth in vitro and in vivo. Overall, our study revealed for the first time a cis-regulatory mechanism of super-enhancer translocation in ETV6::ACSL6 ALL, leading to ALL-accompanying clinical syndrome. These findings may stimulate novel treatment approaches for this challenging ALL subtype.

Prognostic impact of CEBPA mutational subgroups in adult AML.

Despite recent refinements in the diagnostic and prognostic assessment of CEBPA mutations in AML, several questions remain open, i.e. implications of different types of basic region leucin zipper (bZIP) mutations, the role of co-mutations and the allelic state. Using pooled primary data analysis on 1010 CEBPA-mutant adult AML patients, a comparison was performed taking into account the type of mutation (bZIP: either typical in-frame insertion/deletion (InDel) mutations (bZIPInDel), frameshift InDel or nonsense mutations inducing translational stop (bZIPSTOP) or single base-pair missense alterations (bZIPms), and transcription activation domain (TAD) mutations) and the allelic state (single (smCEBPA) vs. double mutant (dmCEBPA)). Only bZIPInDel patients had significantly higher rates of complete remission and longer relapse free and overall survival (OS) compared with all other CEBPA-mutant subgroups. Moreover, co-mutations in bZIPInDel patients (e.g. GATA2, FLT3, WT1 as well as ELN2022 adverse risk aberrations) had no independent impact on OS, whereas in non-bZIPInDel patients, grouping according to ELN2022 recommendations added significant prognostic information. In conclusion, these results demonstrate bZIPInDel mutations to be the major independent determinant of outcome in CEBPA-mutant AML, thereby refining current classifications according to WHO (including all dmCEBPA and smCEBPA bZIP) as well as ELN2022 and ICC recommendations (including CEBPA bZIPms).

Bone marrow-derived mesenchymal stromal cells obstruct AML-targeting CD8+ clonal effector and CAR T-cell function while promoting a senescence-associated phenotype.

Bone marrow mesenchymal stromal cells (MSCs) have been described as potent regulators of T-cell function, though whether they could impede the effectiveness of immunotherapy against acute myeloid leukemia (AML) is still under investigation. We examine whether they could interfere with the activity of leukemia-specific clonal cytotoxic T-lymphocytes (CTLs) and chimeric antigen receptor (CAR) T cells, as well as whether the immunomodulatory properties of MSCs could be associated with the induction of T-cell senescence. Co-cultures of leukemia-associated Wilm's tumor protein 1 (WT1) and tyrosine-protein kinase transmembrane receptor 1 (ROR1)-reactive CTLs and of CD123-redirected switchable CAR T cells were prepared in the presence of MSCs and assessed for cytotoxic potential, cytokine secretion, and expansion. T-cell senescence within functional memory sub-compartments was investigated for the senescence-associated phenotype CD28-CD57+ using unmodified peripheral blood mononuclear cells. We describe inhibition of expansion of AML-redirected switchable CAR T cells by MSCs via indoleamine 2,3-dioxygenase 1 (IDO-1) activity, as well as reduction of interferon gamma (IFNγ) and interleukin-2 (IL-2) release. In addition, MSCs interfered with the secretory potential of leukemia-associated WT1- and ROR1-targeting CTL clones, inhibiting the release of IFNγ, tumor necrosis factor alpha, and IL-2. Abrogated T cells were shown to retain their cytolytic activity. Moreover, we demonstrate induction of a CD28loCD27loCD57+KLRG1+ senescent T-cell phenotype by MSCs. In summary, we show that MSCs are potent modulators of anti-leukemic T cells, and targeting their modes of action would likely be beneficial in a combinatorial approach with AML-directed immunotherapy.

VEXAS syndrome: complete molecular remission after hypomethylating therapy.

The VEXAS syndrome, a genetically defined autoimmune disease, associated with various hematological neoplasms has been attracting growing attention since its initial description in 2020. While various therapeutic strategies have been explored in case studies, the optimal treatment strategy is still under investigation and allogeneic cell transplantation is considered the only curative treatment. Here, we describe 2 patients who achieved complete molecular remission of the underlying UBA1 mutant clone outside the context of allogeneic HCT. Both patients received treatment with the hypomethylating agent azacitidine, and deep molecular remission triggered treatment de-escalation and even cessation with sustained molecular remission in one of them. Prospective studies are necessary to clarify which VEXAS patients will benefit most from hypomethylating therapy and to understand the variability in the response to different treatment strategies.

Allogeneic hematopoietic stem cell transplantation in patients aged 60-79 years in Germany (1998-2018): a registry study.

Incidences of diseases treated with transplantation frequently peak at higher age. The contribution of age to total risk of transplantation has not been estimated amidst an aging society. We compare outcomes of 1,547 patients aged 70-79 years and 9,422 patients aged 60-69 years transplanted 1998-2018 for myeloid, lymphoid and further neoplasia in Germany. To quantify the contribution of population mortality to survival, we derive excess mortality based on a sex-, year- and agematched German population in a multistate model that incorporates relapse and graft-versus-host-disease (GvHD). Overall survival, relapse-free survival (RFS) and GvHD-free-relapse-free survival (GRFS) is inferior in patients aged 70-79 years, compared to patients aged 60-69 years, with 36% (95% Confidence Interval [CI]: 34-39%) versus 43% (41-44%), 32% (30- 35%) versus 36% (35-37%) and 23% (21-26%) versus 27% (26-28%) three years post-transplant (P<0.001). Cumulative incidences of relapse at three years are 27% (25-30%) for patients aged 70-79 versus 29% (29-30%) (60-69 years) (P=0.71), yet the difference in non-relapse mortality (NRM) (40% [38-43%] vs. 35% [34-36%] in patients aged 70-79 vs. 60-69 years) (P<0.001) translates into survival differences. Median OS of patients surviving >1 year relapse-free is 6.7 (median, 95% CI: 4.5-9.4, 70-79 years) versus 9 (8.4-10.1, 60-69 years) years since landmark. Three years after RFS of one year, excess NRM is 14% (95% CI: 12-18%) in patients aged 70-79 versus 12% [11-13%] in patients aged 60-69, while population NRM is 7% (6-7%) versus 3% (3-3%). Mortality for reasons other than relapse, GvHD, or age is as high as 27% (24-29%) and 22% (22-23%) four years after transplantation. In conclusion, survival amongst older patients is adequate after allogeneic stem cell transplantation.

Autologous-allogeneic versus autologous tandem stem cell transplantation and maintenance therapy with thalidomide for multiple myeloma patients less than 60 years of age: a prospective phase II study

The role of autologous-allogeneic tandem stem cell transplantation (alloTSCT) followed by maintenance as upfront treatment for multiple myeloma (MM) is controversial. Between 2008 and 2014 a total of 217 MM patients with a median age of 51 years were included by 20 German centers within an open-label, parallel-group, multi-center clinical trial to compare alloTSCT to auto tandem transplantation TSCT (autoTSCT) followed by a 2-year maintenance therapy with thalidomide (100 mg/d) in both arms with respect to relapse/progression-free survival (PFS) and other relevant outcomes. A total of 178 patients underwent second SCT (allo n = 132 and auto n = 46). PFS at 4 years after the second SCT was 47% (CI: 38-55%) for alloTSCT and 35% (CI: 21-49%) for autoTSCT (p = 0.26). This difference increased to 22% at 8 years (p = 0.10). The cumulative incidences of non-relapse mortality (NRM) and of relapse at 4 years were 13% (CI: 8-20%) and 2% (CI: 0.3-2%) (p = 0.044) and 40% (CI: 33-50%) and 63% (CI: 50-79%) for alloTSCT and autoTSCT (p = 0.04), respectively. The difference for relapse/progression increased to 33% (alloTSCT: 44%, autoTSCT: 77%) at a median follow-up of 82 months (p = 0.002). Four-year OS was 66% (CI: 57-73%) for alloTSCT and 66% (CI: 50-78%) for auto TSCT (p = 0.91) and 8-year OS was 52% and 50% (p = 0.87), respectively. AlloTSCT followed by thalidomide maintenance reduced the rate of recurrence or progression during a follow-up period of up to 10 years but failed to improve PFS significantly.

Ex vivo drug response profiling for response and outcome prediction in hematologic malignancies: the prospective non-interventional SMARTrial.

Ex vivo drug response profiling is a powerful tool to study genotype-drug response associations and is being explored as a tool set for precision medicine in cancer. Here we conducted a prospective non-interventional trial to investigate feasibility of ex vivo drug response profiling for treatment guidance in hematologic malignancies (SMARTrial, NCT03488641 ). The primary endpoint to provide drug response profiling reports within 7 d was met in 91% of all study participants (N = 80). Secondary endpoint analysis revealed that ex vivo resistance to chemotherapeutic drugs predicted chemotherapy treatment failure in vivo. We confirmed the predictive value of ex vivo response to chemotherapy in a validation cohort of 95 individuals with acute myeloid leukemia treated with daunorubicin and cytarabine. Ex vivo drug response profiles improved ELN-22 risk stratification in individuals with adverse risk. We conclude that ex vivo drug response profiling is clinically feasible and has the potential to predict chemotherapy response in individuals with hematologic malignancies beyond clinically established genetic markers.

Successful Combination of Olaparib and 225Ac-Dotatate in a Patient with Neuroendocrine Tumor G3 and BRCA Mutation.

Based on the results of the NETTER-1 trial, peptide receptor radionuclide therapy with Lutetium-177 (177Lu) - DOTATATE is authorized for the treatment of neuroendocrine tumors (NET) grade 1 (G1) and grade 2 (G2) of the intestine. After the failure of 177Lu-DOTATATE therapy, targeted alpha-particle therapy (TAT) may be a possible treatment option. Here, we present a patient with cancer of unknown primary NET G2 later G3. The patient was referred to our hospital with urosepsis due to a second-degree urinary retention. After stent insertion, a contrast-enhanced computed tomography revealed a huge pelvic tumor without metastases. Initially, the patient had undergone surgical treatment. Later the patient developed liver metastasis and was treated by 177Lu-DOTATATE therapy and four lines of systemic therapy. A disease progression was observed and with the knowledge of a germline BRCA1 mutation, the patient was treated with TAT (Actinium-225 [225Ac]-DOTATATE) combined with olaparib. The patient achieved a significant treatment response for 12 months indicating that a combination therapy with an alpha emitter and olaparib demands further investigations in clinical trials.

Steady-state versus chemotherapy-based hematopoietic cell mobilization after anti-CD38-based induction therapy in newly diagnosed multiple myeloma.

BACKGROUND: The incorporation of anti-CD38 monoclonal antibodies (mAb) in induction regimens of newly diagnosed transplant-eligible multiple myeloma (MM) patients has been established as a new standard. However, the optimal strategy of stem cell mobilization in this context is not yet clear. STUDY DESIGN AND METHODS: From May 2020 till September 2022, we retrospectively reviewed patients receiving anti-CD38 mAb-based induction therapy followed by stem cell mobilization either in a steady-state protocol (SSM) using 10 µg/kg granulocyte colony-stimulating factor (G-CSF) for 5 days or in a chemotherapy-based protocol (CM) using 1-4 g/m2 cyclophosphamide and G-CSF. RESULTS: Overall, 85 patients (median age 61 years) were included in the analysis. In total, 90 mobilization attempts were performed, 42 with SSM and 48 with CM. There was no significant difference in the median concentration of CD34+ cells in peripheral blood (PB) prior to apheresis between SSM and CM (61/µL vs. 55.4/µL; p = .60). Cumulative CD34+ yields did not differ between the groups with median of 6.68 and 6.75 × 106 /kg body weight, respectively (p = .35). The target yield (≥4 × 106 CD34+ cells/kg body weight) was reached in 88% (CM) and 86% (SSM), with a high proportion even after a single apheresis session (76% vs. 75%). Plerixafor was found to be more frequently used in SSM (52%) than in CM (23%; p < .01). A total of 83 patients underwent autologous transplantation and all were engrafted. CONCLUSIONS: Stem cell collection in patients undergoing anti-CD38-based induction therapy is feasible with either CM or SSM, although SSM more frequently requires plerixafor.