-
1.
Hematopoietic cell transplantation utilization and outcomes for primary plasma cell leukemia in the current era
Dhakal, B., Patel, S., Girnius, S., Bachegowda, L., Fraser, R., Davila, O., Kanate, A. S., Assal, A., Hanbali, A., Bashey, A., et al
Leukemia. 2020
Abstract
The outcomes of patients with primary plasma cell leukemia (pPCL) after undergoing hematopoietic cell transplantation (HCT) in the novel agent era are unknown. We report outcomes of 348 patients with pPCL receiving autologous (auto-) HCT (n = 277) and allogeneic (allo-) HCT (n = 71) between 2008 and 2015. Median age was 60 years and 56 years for auto- and allo-HCT respectively. For auto-HCT, the 4-year outcomes were: non-relapse mortality (NRM) 7% (4-11%), relapse (REL) 76% (69-82%), progression-free survival (PFS) 17% (13-23%), and overall survival (OS) 28% (22-35%). Karnofsky performance status (KPS) > 90 and ≥very good partial response (VGPR) predicted superior OS in multi-variate analysis for auto-HCT. For allo-HCT, the 4-year outcomes were: NRM 12% (5-21%), REL 69% (56-81%), PFS 19% (10-31%), and OS 31% (19-44%). Compared with prior CIBMTR pPCL patients (1995-2006), inferior survival was noted in the current cohort (3-year OS, 39% vs. 38% in allo-HCT, and 62% vs. 35% in auto-HCT) respectively. However, we noted an increased HCT utilization, from 12% (7-21%) in 1995 to 46% (34-64%) in 2009 using SEER data (available till 2009). Despite modern induction translating to higher proportion receiving HCT, the outcomes remain poor in pPCL patients, mainly derived by high relapse rates post-HCT.
-
2.
Impact of T-cell dose on the outcome of T-cell replete HLA matched allogeneic peripheral blood stem cell transplantation
Saad, A., Lamb, L., Wang, T., Hemmer, M. T., Spellman, S., Couriel, D., Alousi, A., Pidala, J., Abdel-Azim, H., Agrawal, V., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
-
-
-
Free full text
-
Editor's Choice
Abstract
BACKGROUND Data on whether T-cell dose of allogeneic peripheral blood stem cell (PBSC) product influences transplant outcome are conflicting. METHODS Using CIBMTR database, we identified 2,736 adult patients who underwent first allogeneic peripheral blood stem cell (PBSC) transplant for acute leukemia (AML, ALL) or myelodysplastic syndrome (MDS) between 2008-2014 using an HLA-matched sibling donor (MSD) or 8/8-matched unrelated donor (MUD). We excluded ex-vivo and in-vivo T-cell depleted transplants. Correlative analysis was performed between CD3+ T-cell dose and risk of graft-versus-host-disease (GVHD), relapse, non-relapse mortality (NRM), disease free survival (DFS) and overall survival (OS). RESULTS Using maximum likelihood estimation method, we identified CD3+ T-cell cell dose cutoff that separated risk of acute GVHD (aGVHD) grade II-IV in both MSD and MUD groups. A CD3+ T-cell dose cutoff of 14x10(7) cells/kg identified MSD/low CD3+ (n=223) and MSD/high CD3+ (n=1214), and a dose of 15x10(7) cells/kg identified MUD/low CD3+ (n=197) and MUD/high CD3+ (n=1102). With univariate analysis, MSD/high CD3+ group had higher cumulative incidence of day 100 aGVHD grade II-IV of 33% vs 25% when compared to MSD/low CD3+ group (P value =0.009). There was no other difference between both groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. MUD/high CD3+ group had higher cumulative incidence of day 100 aGVHD grade II-IV of 49% vs 41% when compared to MUD/low CD3+ group (P value =0.04). There was no other difference between both groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of MSD and MUD groups failed to show an association between CD3+ T-cell dose and risk of either aGVHD grade II-IV (p value =0.1 and 0.07 respectively) or cGVHD (p value=0.8 and 0.3 respectively). Sub-analysis of CD4, CD8 and CD4/CD8 ratio failed to identify cutoff values predictive of transplant outcome. Using log-rank test, the sample size was, however, suboptimal to identify difference at these cutoff cell dose. CONCLUSION In this registry study, CD3+ T-cell dose of PBSCT product did not influence risk of aGVHD or cGVHD or other transplant outcomes when using HLA-matched sibling or 8/8 unrelated donors. Subset analysis of CD4+ and CD8+ T-cell dose was not possible for small sample size.
PICO Summary
Population
Patients reported to CIBMTR database with acute leukaemia (ALL or AML) or myelodysplastic syndrome between 2008-2014 (n=2736)
Intervention
First allogeneic peripheral blood stem cell using an HLA-matched sibling donor (MSD)
Comparison
8/8-matched unrelated donor (MUD)
Outcome
Using maximum likelihood estimation method, we identified CD3+ T-cell cell dose cutoff that separated risk of acute GVHD (aGVHD) grade II-IV in both MSD and MUD groups. A CD3+ T-cell dose cutoff of 14x10(7) cells/kg identified MSD/low CD3+ (n=223) and MSD/high CD3+ (n=1214), and a dose of 15x10(7) cells/kg identified MUD/low CD3+ (n=197) and MUD/high CD3+ (n=1102). With univariate analysis, MSD/high CD3+ group had higher cumulative incidence of day 100 aGVHD grade II-IV of 33% vs 25% when compared to MSD/low CD3+ group. MUD/high CD3+ group had higher cumulative incidence of day 100 aGVHD grade II-IV of 49% vs 41% when compared to MUD/low CD3+ group. Multivariate analysis of MSD and MUD groups failed to show an association between CD3+ T-cell dose and risk of either aGVHD grade II-IV or cGVHD. Sub-analysis of CD4, CD8 and CD4/CD8 ratio failed to identify cutoff values predictive of transplant outcome.
-
3.
Maintenance Therapies for Hodgkin and Non-Hodgkin Lymphomas After Autologous Transplantation: A Consensus Project of ASBMT, CIBMTR, and the Lymphoma Working Party of EBMT
Kanate, A. S., Kumar, A., Dreger, P., Dreyling, M., Le Gouill, S., Corradini, P., Bredeson, C., Fenske, T. S., Smith, S. M., Sureda, A., et al
JAMA oncology. 2019
-
-
Free full text
-
Abstract
Importance: Maintenance therapies are often considered as a therapeutic strategy in patients with lymphoma following autologous hematopoietic cell transplantation (auto-HCT) to mitigate the risk of disease relapse. With an evolving therapeutic landscape, where novel drugs are moving earlier in therapy lines, evidence relevant to contemporary practice is increasingly limited. The American Society for Blood and Marrow Transplantation (ASBMT), Center for International Blood and Marrow Transplant Research (CIBMTR), and European Society for Blood and Marrow Transplantation (EBMT) jointly convened an expert panel with diverse expertise and geographical representation to formulate consensus recommendations regarding the use of maintenance and/or consolidation therapies after auto-HCT in patients with lymphoma. Observations: The RAND-modified Delphi method was used to generate consensus statements where at least 75% vote in favor of a recommendation was considered as consensus. The process included 3 online surveys moderated by an independent methodological expert to ensure anonymity and an in-person meeting. The panel recommended restricting the histologic categories covered in this project to Hodgkin lymphoma (HL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma. On completion of the voting process, the panel generated 22 consensus statements regarding post auto-HCT maintenance and/or consolidation therapies. The grade A recommendations included endorsement of: (1) brentuximab vedotin (BV) maintenance and/or consolidation in BV-naive high-risk HL, (2) rituximab maintenance in MCL undergoing auto-HCT after first-line therapy, (3) rituximab maintenance in rituximab-naive FL, and (4) No post auto-HCT maintenance was recommended in DLBCL. The panel also developed consensus statements for important real-world clinical scenarios, where randomized data are lacking to guide clinical practice. Conclusions and Relevance: In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a rigorous framework for developing consensus recommendations for post auto-HCT maintenance and/or consolidation therapies in lymphoma.
-
4.
Lower GVHD and relapse risk in PTCy-based Haploidentical vs Matched Sibling Donor RIC Transplant for Hodgkin Lymphoma
Ahmed, S., Kanakry, J. A., Ahn, K. W., Litovich, C., Abdel-Azim, H., Aljurf, M., Bacher, V. U., Bejanyan, N., Cohen, J. B., Farooq, U., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
-
-
-
Free full text
-
Editor's Choice
Abstract
Classical Hodgkin lymphoma (cHL) patients with relapsed or refractory disease may benefit from allogeneic hematopoietic cell transplantation (allo-HCT), but many lack a matched sibling donor (MSD). Herein, we compare outcomes of two reduced-intensity conditioning (RIC) HCT platforms in cHL: T cell-replete related donor haploidentical (haplo) HCT with post-transplantation cyclophosphamide (PTCy)-based approach versus MSD/calcineurin inhibitor (CNI)-based approach. The study included 596 adult patients who underwent a first RIC allo-HCT for cHL between 2008-2016, using either haplo-PTCy (n=139) or MSD/CNI-based (n=457) approach. Overall survival (OS) was the primary endpoint. Secondary endpoints included acute (a) and (c) graft-versus-host disease (GVHD), non-relapse mortality (NRM), relapse/progression, and progression-free survival (PFS). On multivariate analysis, there was no significant difference between haplo/PTCy and MDS/CNI-based approaches in terms of OS (hazard ratio [HR]=1.07; 95%CI=0.79-1.45; p=0.66) or PFS (HR=0.86; 95%CI=0.68-1.10; p=0.22). Haplo/PTCy was associated with a significantly higher risk of grade 2-4 aGVHD (odds ratio [OR]=1.73, 95%CI=1.16-2.59, p=0.007), but the risk of grade 3-4 aGVHD was not significantly different between the two cohorts (OR=0.61, 95%CI=0.29-1.27, p=0.19). The haplo/PTCy platform provided a significant reduction in cGVHD risk (HR=0.45, 95%CI=0.32-0.64, p<0.001), and a significant reduction in relapse risk (HR=0.74, 95%CI=0.56-0.97, p=0.03). There was a statistically non-significant trend towards higher NRM with haplo/PTCy approach (HR=1.65, 95%CI=0.99-2.77, p=0.06). Haplo/PTCy-based approaches are associated with lower incidence of cGVHD and relapse, with PFS and OS outcomes comparable to MSD/CNI-based approaches. There was a leaning towards higher NRM with haplo/PTCy-based platform. These data show that haplo/PTCy allo-HCT in cHL results in survival comparable to MSD/CNI-based allo-HCT.
PICO Summary
Population
Adult patients who underwent a first RIC allo-HCT for classical Hodgkin lymphoma between 2008-2016 (n=596)
Intervention
T cell-replete related donor haploidentical HCT with post-transplantation cyclophosphamide (Haplo/PTCy) (n=139)
Comparison
Matched Sibling Donor with calcineurin inhibitor (MSD/CNI) (n=457)
Outcome
On multivariate analysis, there was no significant difference between Haplo/PTCy and MSD/CNI-based approaches in terms of overall survival or progression-free survival. Haplo/PTCy was associated with a significantly higher risk of grade 2-4 aGVHD, but the risk of grade 3-4 aGVHD was not significantly different between the two cohorts. The haplo/PTCy platform provided a significant reduction in cGVHD risk, and a significant reduction in relapse. There was a statistically non-significant trend towards higher NRM with haplo/PTCy approach.
-
5.
The Outcome of Haplo-Identical Transplantation in Patients with Relapsed Multiple Myeloma: An EBMT/CIBMTR Report
Sahebi, F., Garderet, L., Kanate, A. S., Eikema, D. J., Knelange, N. S., Alvelo, O. F. D., Koc, Y., Blaise, D., Bashir, Q., Moraleda, J. M., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
-
-
Free full text
-
Editor's Choice
Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) using siblings and matched donors has the potential for long-term disease control in a subset of high-risk multiple myeloma (MM) patients. However, the data on using haploidentical donors in this disease are limited. We conducted a retrospective analysis to examine the outcomes of patients with MM who underwent haploidentical allo-HCT within EBMT/CIBMTR centers. A total of 96 patients underwent haploidentical transplantation between 2008 and 2016. With a median follow up of 24.0 months (range, 13.2-24.9 months), 97% (95%CI, 93%-100%) of patients had neutrophil engraftment by day 28, and 75% (95%CI, 66%-84%) achieved platelet recovery by day 60. Two-year progression-free survival (PFS) was 17% (95%CI, 8%-26%), and overall survival (OS) was 48% (95%CI, 36%-59%). At 2 years, the cumulative risk of relapse/progression was 56% (95%CI, 45%-67%), and 1-year non-relapse mortality (NRM) was 21% (95%CI, 13%-29%). The incidence of acute graft-versus-host-disease (GVHD) grades II-IV by 100 days and chronic GVHD at 2 years were 39% (95%CI, 28%-49%) and 46% (95%CI, 34%-59%), respectively. On univariate analysis, use of post-transplant cyclophosphamide (PT-Cy) (54% [95%CI, 41%-68%] vs 25% [95%CI, 1%-48%], p=0.009), and use of bone marrow as source of stem cells (72% [95%CI, 55%-89%] vs 31% [95%CI, 17%-46%], p=0.001), were associated with improved OS at 2 years. Disease status, patient gender, intensity of conditioning regimen, recipient/donor gender mismatch, and CMV status had no impact on OS, PFS, or NRM. Haploidentical transplantation is feasible for patients with multiply relapsed or high-risk MM, with an encouraging 2-year OS of 48% and an NRM rate of 21% at 1 year, supporting further investigation of haploidentical transplantation in suitable candidates with MM.
-
6.
Survival of Lymphoma Patients Experiencing Relapse or Progression after an Allogeneic Hematopoietic Cell Transplantation
Epperla, N., Hamadani, M., Ahn, K. W., He, F., Kodali, D., Kleman, A., Hari, P. N., Pasquini, M., Fenske, T. S., Craig, M. D., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
BACKGROUND Outcome and management of patients who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) has evolved in a recent decade. Using a multi-institutional retrospective database, we report the predictive factors and survival of lymphoma patients who relapse following allo-HCT. METHODS We evaluated 495 allo-HCT recipients transplanted between 2000-2015 at three academic US medical centers. Landmark analysis evaluating predictive factors was performed at 1-month post allo-HCT relapse with primary end-point of post-relapse overall survival (PR-OS). RESULTS A total of 175 lymphoma patients (35%) experienced relapse post allo-HCT. Of these, 126 patients at the median age of 46 years (range 19-71 years) were evaluable. Most patients (86%) received subsequent therapy; 80 patients received targeted agents and 19 donor lymphocyte infusion. On univariate analysis, median PR-OS for patients with Hodgkin lymphoma was 47.9 months compared to 11.3 months in patients with indolent and 10.1 months in aggressive non-Hodgkin lymphoma (p=0.04). On multivariate analysis, post-relapse therapy administration (no therapy vs targeted therapy: HR=0.21, 95%CI=0.10-0.45; no therapy vs non-targeted therapy: HR=0.26, 95%CI=0.11-0.57), late relapse after 130 days post allo-HCT (relative to early relapse, HR 0.25; p<0.001) and ECOG performance status of 0-1 (vs ECOG ≥ 2, HR 0.49; p=0.003) were associated with a significantly reduced risk of mortality. Patients relapsing ≥130 days from the time of allo-HCT yield PR-OS of 48.8 months compared to 6.5 months in patients with early relapse (p<0.001). CONCLUSIONS Our data suggest that in the contemporaneous era, therapies used for patients experiencing post allo-HCT lymphoma relapse can extend survival.
-
7.
Allogeneic haematopoietic cell transplantation for extranodal natural killer/T-cell lymphoma, nasal type: a CIBMTR analysis
Kanate, A. S., DiGilio, A., Ahn, K. W., Al Malki, M., Jacobsen, E., Steinberg, A., Hamerschlak, N., Kharfan-Dabaja, M., Salit, R., Ball, E., et al
British journal of haematology. 2018;182(6):916-920
Clinical Commentary
Next
What is known?
NIHMS891405
What did this paper set out to examine?
What did they show?
What are the implications for practice and for future work?
-
8.
Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia
Chhabra, S., Ahn, K. W., Hu, Z. H., Jain, S., Assal, A., Cerny, J., Copelan, E. A., Daly, A., DeFilipp, Z., Gadalla, S. M., et al
Blood advances. 2018;2(21):2922-2936
-
-
Free full text
-
-
Editor's Choice
Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era.
-
9.
Patterns of Relapse after Salvage Autologous Stem Cell Transplant for Hodgkin's Lymphoma: Should Sites of Relapse Relative to Initially Involved Sites Be Used to Guide Indications for Peri-transplant Radiotherapy
Farris, J. C., Ritter, A., Craig, M. D., Shah, N., Veltri, L., Kanate, A. S., Ross, K., Vargo, J. A.
Practical radiation oncology. 2018
Abstract
PURPOSE We aimed to assess patterns of relapse in patients undergoing salvage ASCT for relapsed HL in the modern-era with the hypothesis that patients suffering relapse at initially involved sites are at increased risks of relapse post-ASCT that may help guide the application of peri-transplant RT. MATERIALS/METHODS A retrospective review of 38 patients undergoing ASCT from 2002-2017 for relapsed or refractory HL. Site of relapse at time of ASCT and subsequent relapse were compared to sites of initial involvement at diagnosis using follow-up imaging most commonly PET/CT. Relapse and overall survival were calculated from the date of ASCT using the Kaplan Meier method with multivariate analysis completed using Cox multivariate analysis. RESULTS The median follow-up was 38 months [Interquartile Range (IQR): 18-66 months]. Twenty-two patients (58%) suffered relapse following ASCT at a median time to relapse of 9.1 months (IQR: 2.9 -12.3) with a 5-year risk of relapse of 58% (95%CI: 41-75%). On univariate analysis, relapse at an initially involved site was significant for higher rates of relapse at 71% at 5-years (95% CI: 52-90%) compared to relapse at initially uninvolved sites 30% (95% CI: 2-58%), p=0.05. Relapse rate was also significantly higher in patients less than 30 years old at diagnosis at 80% (95% CI: 59-100%) compared to 40% (95% CI: 18-62%) at 5-years in patients greater than 30 years of age (p<0.01). On multivariate analysis, relapse at initially involved sites was significant for higher rates of relapse, HR 8.3 (95% CI: 1.2-57.4, p=0.03) CONCLUSIONS Relapse at initially involved sites may potentially increase risks of relapse after ASCT and additional studies are needed to clarify if this should be used as an additional factor to guide recommendations for peri-transplant RT.
-
10.
Revised-International Staging System (R-ISS) is Predictive and Prognostic for Early Relapse (<24 months) after Autologous Transplantation for Newly Diagnosed Multiple Myeloma (MM)
Gopalakrishnan, S., D'Souza, A., Scott, E., Fraser, R., Davila, O., Shah, N., Gale, R. P., Kamble, R., Diaz, M. A., Lazarus, H. M., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
The Revised International Staging System (R-ISS) combines ISS with genetic markers and lactate dehydrogenase, and can prognosticate newly diagnosed multiple myeloma (MM). Early relapse (<24 months) after upfront autologous hematopoietic cell transplantation (AHCT) strongly predicts inferior overall survival (OS). We examined the ability of R-ISS in predicting early relapse and its independent prognostic effect on post-relapse survival after an early relapse. Using the Center for International Blood and Marrow Transplant Research database, we identified MM patients receiving first AHCT within 18 months after diagnosis with available R-ISS stage at diagnosis (n= 628). Relative risks of relapse/progression, progression-free survival (PFS) and OS were calculated with R-ISS group as a predictor in multivariate analysis. Among early relapsers, post-relapse survival was tested to identify factors affecting post-relapse OS. The cumulative incidence of early relapse was 23%, 39% and 50% for R-ISS I, R-ISS II and R-ISS III, respectively (p <0.001). Shorter PFS and OS were seen with higher stage R-ISS. R-ISS was independently predictive for inferior post-relapse OS among early relapsers, as was the presence of ≥3 comorbidities and the use of ≥2 induction chemotherapy lines. R-ISS stage at diagnosis predicts early post-AHCT relapse and independently affects post-relapse survival among early relapsers.