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Impact of age, obesity, and renal impairment on outcomes after autologous stem cell transplantation for patients with newly diagnosed multiple myeloma
Gaffney, K. J., Bakos, J. K., Velayati, A., Davis, J. A., Thurlapati, A., Weeda, E., Maldonado, A., Granger, K., Butcher, C., Herrington, T., et al
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners. 2024;:10781552231224361
Abstract
INTRODUCTION There remains a need to determine whether certain subgroups of newly diagnosed multiple myeloma (NDMM) derive the same benefit from high-dose chemotherapy-autologous stem cell transplant (HDT-ASCT). We describe our institutional experience highlighting the impact of age, obesity, and renal impairment on outcomes after HDT-ASCT for patients with NDMM in a real-world setting. METHODS A total of 449 consecutive patients were included in this retrospective analysis. RESULTS No difference in median progression free survival or overall survival was seen for patients with age > 65, body mass index (BMI) > 30 kg/m(2), or estimated glomerular filtration rate < 60 mL/min/1.73 m(2) when compared to those without these characteristics. From a safety standpoint, there were no differences in the incidence of transplant-related mortality or secondary malignancy among subgroups. CONCLUSION For patients with NDMM undergoing HDT-ASCT, there is no difference in outcomes based on age, BMI, or renal function, and the presence of one or more of these factors should not preclude patients from HDT-ASCT.
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Ofatumumab as part of reduced intensity conditioning in high risk B-cell lymphoma patients: final long-term analysis from a prospective multicenter Phase-II Trial
Cabrero, M., López-Corral, L., Jarque, I., de la Cruz-Vicente, F., Pérez-López, E., Valcárcel, D., Sanz, J., Espigado, I., Ortí, G., Martín-Calvo, C., et al
Bone marrow transplantation. 2024
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Editor's Choice
Abstract
Curative potential of allogeneic transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (NHL) could be enhanced by the integration of Ofatumumab (OFA), a 2nd generation anti-CD20 moAb, due to an antitumor effect and a role over graft-versus-host disease (GVHD). In this phase II trial (NCT01613300), we investigated safety and effectiveness of OFA-based reduced intensity conditioning (RIC). High-risk B-cell NHL patients with chemorrefractory disease or post-autologous SCT relapse were eligible. OFA was added to a standard RIC regimen. Primary endpoint was grade 3-4 aGVHD rate, while secondary endpoints included CR and survival rates. Thirty-three patients were included (median age 51; diffuse large B-cell:68%, HLA-identical donor: 74%). No grade >2 OFA toxicity was observed. Acute GVHD affected 77% of patients (16% grade 3-4). Remarkably, GVHD achieved CR in 75% of patients after first-line treatment. Chronic GVHD, primarily mild or moderate, occurred in 54% of patients. NHL CR rate at day +100 was 81%. Relapses occurred in 7 patients after a median of 3 months. Causes of death were lymphoma progression (5), infections (10), and GVHD (2). At 24 months, progression-free and overall survival rates were 50.1 and 51.6% respectively. OFA-RIC regimen is safe and effective, though acute GVHD remains a significant complication. However, data suggest that OFA could mitigate its severity.
PICO Summary
Population
Adults with high-risk B-cell non-Hodgkin lymphoma with either chemorrefractory disease or who relapsed post-autologous transplant, from centres in Spain (n=33)
Intervention
Ofatumumab (OFA), a 2nd generation anti-CD20 moAb, added to a reduced intensity conditioning (RIC) regime
Comparison
None
Outcome
Acute GVHD affected 77% of patients (16% grade 3-4). Remarkably, GVHD achieved CR in 75% of patients after first-line treatment. Chronic GVHD, primarily mild or moderate, occurred in 54% of patients. NHL CR rate at day +100 was 81%. Relapses occurred in 7 patients after a median of 3 months. Causes of death were lymphoma progression (5), infections (10), and GVHD (2). At 24 months, progression-free and overall survival rates were 50.1 and 51.6% respectively.
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Allogeneic hematopoietic cell transplantation is equally effective in secondary acute lymphoblastic leukemia (ALL) compared to de-novo ALL-a report from the EBMT registry
Sadowska-Klasa, A., Zaucha, J. M., Labopin, M., Bourhis, J. H., Blaise, D., Yakoub-Agha, I., Salmenniemi, U., Passweg, J., Fegueux, N., Schroeder, T., et al
Bone marrow transplantation. 2024
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Editor's Choice
Abstract
Secondary acute lymphoblastic leukemia (s-ALL) comprises up to 10% of ALL patients. However, data regarding s-ALL outcomes is limited. To answer what is the role of allogeneic hematopoietic cell transplantation (HCT) in s-ALL, a matched-pair analysis in a 1:2 ratio was conducted to compare outcomes between s-ALL and de novo ALL (dn-ALL) patients reported between 2000-2021 to the European Society for Blood and Marrow Transplantation registry. Among 9720 ALL patients, 351 (3.6%) were s-ALL, of which 80 were in first complete remission (CR1) with a known precedent primary diagnosis 58.8% solid tumor (ST), 41.2% hematological diseases (HD). The estimated 2-year relapse incidence (RI) was 19.1% (95%CI: 11-28.9), leukemia-free survival (LFS) 52.1% (95%CI: 39.6-63.2), non-relapse mortality (NRM) 28.8% (95%CI: 18.4-40), GvHD-free, relapse-free survival (GRFS) 39.4% (95%CI: 27.8-50.7), and overall survival (OS) 60.8% (95%CI: 47.9-71.4), and did not differ between ST and HD patients. In a matched-pair analysis, there was no difference in RI, GRFS, NRM, LFS, or OS between s-ALL and dn-ALL except for a higher incidence of chronic GvHD (51.9% vs. 31.4%) in s-ALL. To conclude, patients with s-ALL who received HCT in CR1 have comparable outcomes to patients with dn-ALL.
PICO Summary
Population
Adults with acute lymphoblastic leukaemia, reported to the EBMT registry (n=9720)
Intervention
A detailed analysis cohort who were transplanted for secondary acute lymphoblastic leukaemia (s-ALL, n=80)
Comparison
Matched controls who were transplanted for de novo ALL (dn-ALL, n=80)
Outcome
The estimated 2-year relapse incidence (RI) was 19.1% (95%CI: 11-28.9), leukemia-free survival (LFS) 52.1% (95%CI: 39.6-63.2), non-relapse mortality (NRM) 28.8% (95%CI: 18.4-40), GvHD-free, relapse-free survival (GRFS) 39.4% (95%CI: 27.8-50.7), and overall survival (OS) 60.8% (95%CI: 47.9-71.4), and did not differ between solid tumour and haematological disease patients. In a matched-pair analysis, there was no difference in RI, GRFS, NRM, LFS, or OS between s-ALL and dn-ALL except for a higher incidence of chronic GvHD (51.9% vs. 31.4%) in s-ALL.
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Auto-hematopoietic stem cell transplantation or chemotherapy? Meta-analysis of clinical choice for AML
Ge, S., Wang, J., He, Q., Zhu, J., Liu, P., Wang, H., Zhang, F.
Annals of hematology. 2024
Abstract
For patients with acute myeloid leukemia (AML) who are not candidates for allogeneic stem cell transplantation (SCT) or do not have a human leukocyte antigen (HLA)-matched donor, it is unclear whether autologous SCT (ASCT) has a better prognosis after the first complete response (CR1) compared to further chemotherapy treatment. A meta-analysis evaluating ASCT compared to further chemotherapy for AML patients in CR1 was performed. The Medline, Embase, Cochrane Controlled Trials Registry, Cochrane Library, Web of Science, and National Knowledge Infrastructure of China databases were searched for relevant literature as of May 26, 2023. Eligible studies included prospectively enrolled adults with AML and randomized first-time respondent patients who did not have a matched sibling donor. Fourteen randomized controlled trials were identified and included 4281 participants, of which 1499 patients received ASCT and 2782 underwent chemotherapy and continued follow-up. In patients with AML in CR1, a lower relapse rate was associated with ASCT compared to chemotherapy [odds ratio (OR) = 0.49, 95% confidence interval (CI) = 0.41-0.57]. Significant disease-free survival (DFS; OR = 1.37, 95% CI = 1.02-1.84) and relapse-free survival (RFS; OR = 2.78, 95% CI = 1.28-6.02) ASCT benefits were documented, and there was no difference in the overall survival (OS) when the studies were pooled (OR = 1.12, 95% CI = 0.85-1.48). The study results indicated that after the first remission, AML patients receiving autologous stem cell transplantation had higher DFS and RFS, similar OS, and lower relapse compared to patients undergoing chemotherapy treatment. This indicated that autologous stem cell transplantation may have a better prognosis.
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HLA peptide-binding pocket diversity modulates immunological complications after cord blood transplant in acute leukaemia
Boukouaci, W., Rivera-Franco, M. M., Volt, F., Lajnef, M., Wu, C. L., Rafii, H., Cappelli, B., Scigliuolo, G. M., Kenzey, C., Ruggeri, A., et al
British journal of haematology. 2024
Abstract
Pocket motifs and their amino acid positions of HLA molecules are known to govern antigen presentation to effector cells. Our objective was to analyse their influence on the risk of graft-versus-host disease (GVHD) and relapse after umbilical cord blood transplant (UCBT). The transplant characteristics of 849 patients with acute leukaemia were obtained from the Eurocord/EBMT database. Higher acute (a) GVHD was associated with homozygosity of UCB HLA-C amino acid positions 77 and 80 (NN/KK) (p = 0.008). Severe aGVHD was associated with HLA-A pocket B YSAVMENVHY motif (p = 0.002) and NN and RR genotypes of the HLA-C amino acid positions 77 and 156 (p = 0.006 and p = 0.002). Such risk was also increased in case of recipient and UCB mismatches in P4 (p < 0.0001) and P9 (p = 0.003) pockets of HLA-DQB1 alleles. For chronic GVHD, the pocket B YYAVMEISNY motif of the HLA-B*15:01 allele and the absence of mismatch between recipient and UCB in the P6 pocket of HLA-DRB1 were associated with a lower risk (p = 0.0007 and p = 0.0004). In relapse, both UCB pocket B YFAVMENVHY belonging to HLA-A*32:01 and recipient pocket B YDSVGENYQY motif of the HLA-C*07:01 allele were associated with higher risk (p = 0.0026 and p = 0.015). We provide clues on HLA-mediated cellular interactions and their role in the development of GVHD and relapse.
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Allogeneic haematopoietic cell transplantation for therapy-related myeloid neoplasms arising following treatment for lymphoma: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT
Nabergoj, M., Eikema, D. J., Koster, L., Platzbecker, U., Sockel, K., Finke, J., Kröger, N., Forcade, E., Nagler, A., Eder, M., et al
Bone marrow transplantation. 2024
Abstract
Therapy-related myeloid neoplasms (t-MN), either myelodysplastic neoplasms (t-MDS) or acute myeloid leukemias (t-AML), have a poor prognosis and allogeneic haematopoietic cell transplantation (allo-HCT) represents the only curative option. In this multicenter, registry-based study, we analyzed outcomes of 378 patients undergoing first allo-HCT between 2006-2017 for t-MN arising secondary to lymphoma treatment. Median age was 58 years at allo-HCT; 222 (59%) had a diagnosis of t-MDS and 156 (41%) of t-AML, respectively. At the time of allo-HCT, 46% of t-MN cases were reported as in complete remission (CR) and 15% of lymphomas were recorded as not in remission. A reduced intensity conditioning regimen was used in 70% of cases. For the entire cohort, 5-year OS, and t-MN PFS, relapse incidence and NRM were 32%, 28%, 35% and 37%, respectively. In multivariable analysis, undergoing allo-HCT with t-MN not in CR and older age were associated with significantly worse OS, PFS and NRM. At 5 years post allo-HCT, the relapse incidence of lymphoma was low at 3%, while the rate of secondary malignancies was 8%. This analysis shows the curative potential of allo-HCT for patients with t-MN arising secondary to lymphoma treatment in approximately a third of patients.
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Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients With Acute Myeloid Leukemia Harboring KMT2A Rearrangement and Its Prognostic Factors
Jiang, B., Zhao, Y., Luo, Y., Yu, J., Chen, Y., Ye, B., Fu, H., Lai, X., Liu, L., Ye, Y., et al
Cell transplantation. 2024;33:9636897231225821
Abstract
KMT2A rearrangement (KMT2A-r) in patients with acute myeloid leukemia (AML) is associated with poor outcomes; the prognostic factors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain unclear. We investigated 364 adults with AML who underwent allo-HSCT between April 2016 and May 2022, and 45 had KMT2A-r among them. Propensity score analysis with 1:1 matching and the nearest neighbor matching method identified 42 patients in KMT2A-r and non-KMT2A-r cohorts, respectively. The 2-year overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and non-relapsed mortality rates of patients with KMT2A-r (n = 45) were 59.1%, 49.6%, 41.5%, and 8.9%, respectively. Using propensity score matching, the 2-year OS rate of patients with KMT2A-r (n = 42) was lower than that of those without KMT2A-r (n = 42; 56.1% vs 88.1%, P = 0.003). Among patients with KMT2A-r (n = 45), the prognostic advantage was exhibited from transplantation in first complete remission (CR1) and measurable residual disease (MRD) negative, which was reflected in OS, RFS, and CIR (P < 0.001, P < 0.001, and P = 0.002, respectively). Furthermore, patients with AF6 had poorer outcomes than those with AF9, ELL, and other KMT2A-r subtypes (P = 0.032, P = 0.001, and P = 0.001 for OS, RFS, and CIR, respectively). However, no differences were found in the OS, RFS, and CIR between patients with KMT2A-r with and without mutations (all P > 0.05). Univariate and multivariate analyses revealed that achieving CR1 MRD negative before HSCT was a protective factor for OS [hazard ratio (HR) = 0.242, P = 0.007], RFS (HR = 0.350, P = 0.036), and CIR (HR = 0.271, P = 0.021), while AF6 was a risk factor for RFS (HR = 2.985, P = 0.028) and CIR (HR = 4.675, P = 0.004). The prognosis of patients with KMT2A-r AML was poor, particularly those harboring AF6-related translocation; however, it is not associated with the presence of mutations. These patients can benefit from achieving CR1 MRD negative before HSCT.
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Disease Status and Interval between HCTs Predict Outcome of Pediatric Patients who Undergo a Subsequent HCT for Relapsed Hematologic Malignancy
Epperly, R., Li, Y., Selukar, S., Zeng, E., Madden, R., Mamcarz, E., Naik, S., Qudeimat, A., Sharma, A., Talleur, A., et al
Transplantation and cellular therapy. 2024
Abstract
BACKGROUND Patients with hematologic malignancies who relapse after allogeneic hematopoietic cell transplant (HCT) have a poor prognosis. While proceeding to subsequent HCT can provide potential for long-term survival, there is limited data to guide which patients are most likely to benefit and which HCT strategies are best in this heavily pre-treated population. OBJECTIVE The goals of this study were to: i) describe the clinical outcomes of a subsequent HCT in pediatric patients with relapsed hematologic malignancies in a cohort enriched for haploidentical donors, and ii) evaluate the association of patient-, disease-, and treatment-related factors with survival. STUDY DESIGN We retrospectively evaluated patients who underwent a subsequent HCT for management of post-HCT relapse at a single institution between 2000-2021. RESULTS Among 106 patients who received a second allogeneic HCT, one-year event-free survival (EFS) was 34% and one-year overall survival (OS) was 46%, with five-year EFS of 26% and five-year OS of 31%. Only disease-related factors were associated with outcome after second HCT, specifically the interval between HCTs and presence or absence of active disease at the time of HCT. In this cohort, patient- and treatment-related factors were not associated with differences in EFS or OS. Patients receiving a third or fourth HCT (n=13) had comparable survival outcomes to those receiving a second HCT. CONCLUSIONS Our experience highlights that a subsequent HCT has curative potential for a subset of patients who relapse after HCT, including those who receive a subsequent HCT from a haploidentical donor. While relapse and treatment-related toxicities remain major challenges, our study indicates that achieving complete remission prior to subsequent HCTs has the potential to further improve outcomes.
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The impact of social vulnerability index on survival following autologous stem cell transplant for multiple myeloma
Salafian, K., Mazimba, C., Volodin, L., Varadarajan, I., Pilehvari, A., You, W., Knio, Z. O., Ballen, K.
Bone marrow transplantation. 2024
Abstract
Autologous hematopoietic stem cell transplantation (ASCT) is the standard of care for eligible patients with multiple myeloma (MM) to prolong progression-free survival (PFS). While several factors affect survival following ASCT, the impact of social determinants of health such as the CDC Social Vulnerability Index (SVI) is not well documented. This single-center retrospective analysis evaluated the impact of SVI on PFS following ASCT in MM patients. 225 patients with MM who underwent ASCT participated, with 51% transplanted in the last 5 years. At 5 years post-transplant, 55 (50%) achieved PFS and 66 (60%) remained alive. Higher SVI values were significantly associated with lower odds of PFS (OR = 0.521, p < 0.01, 95% CI [0.41, 0.66]) and OS (OR = 0.592, p < 0.01, 95% CI [0.46, 0.76]) post-transplant. Greater vulnerability scores in the socioeconomic status (OR = 0.890; 95% CI: [0.82, 0.96]), household characteristics (OR = 0.912; 95% CI: [0.87, 0.95]), and racial and ethnic minority status (OR = 0.854; 95% CI: [0.81, 0.90]) themes significantly worsened the odds of PFS. These results suggest high SVI areas may need more resources to achieve optimal PFS and OS. Future studies will focus on addressing factors within the socioeconomic status, household characteristics, and racial and ethnic minority subthemes, as these have a more pronounced effect on PFS.
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10.
Droplet digital PCR for sensitive relapse detection in acute myeloid leukaemia patients transplanted by reduced intensity conditioning
Gronlund, J. K., Veigaard, C., Juhl-Christensen, C., Skou, A. S., Melsvik, D., Ommen, H. B.
European journal of haematology. 2024
Abstract
INTRODUCTION Follow-up after allogeneic transplantation in acute myeloid leukaemia (AML) is guided by measurable residual disease (MRD) testing. Quantitative polymerase chain reaction (qPCR) is the preferred MRD platform but unfortunately, 40%-60% of AML patients have no high-quality qPCR target. This study aimed to improve MRD testing by utilising droplet digital PCR (ddPCR). ddPCR offers patient-specific monitoring but concerns of tracking clonal haematopoiesis rather than malignant cells prompt further validation. METHODS Retrospectively, we performed MRD testing on blood and bone marrow samples from AML patients transplanted by reduced-intensity conditioning. RESULTS The applicability of ddPCR was 39/42 (92.9%). Forty-five ddPCR assays were validated with a 0.0089% median sensitivity. qPCR targeting NPM1 mutation detected relapse 46 days before ddPCR (p = .03). ddPCR detected relapse 34.5 days before qPCR targeting WT1 overexpression (p = .03). In non-relapsing patients, zero false positive ddPCR MRD relapses were observed even when monitoring targets associated with clonal haematopoiesis such as DNMT3A, TET2, and ASXL1 mutations. CONCLUSION These results confirm that qPCR targeting NPM1 mutations or fusion transcripts are superior in MRD testing. In the absence of such targets, ddPCR is a promising alternative demonstrating (a) high applicability, (b) high sensitivity, and (c) zero false positive MRD relapses in non-relapsing patients.