by
Muna Qayed;
Tao Wang;
Michael T. Hemmer;
Stephen Spellman;
Mukta Arora;
Daniel Couriel;
Amin Alousi;
Joseph Pidala;
Hisham Abdel-Azim;
Mahmoud Aljurf;
Mouhab Ayas;
Menachem Bitan;
Mitchell Cairo;
Sung Won Choi;
Christopher Dandoy;
David Delgado;
Robert Peter Gale;
Gregory Hale;
Haydar Frangoul;
Rammurti T. Kamble;
Mohamed Kharfan-Dabaja;
Leslie Lehman;
John Levine;
Margaret MacMillan;
David I. Marks;
Taiga Nishihori;
Richard F. Olsson;
Peiman Hematti;
Olov Ringden;
Ayman Saad;
Prakash Satwani;
Bipin N. Savani;
Kirk R. Schultz;
Sachiko Seo;
Shalini Shenoy;
Edmund Waller;
Lolie Yu;
Mary M. Horowitz;
John Horan
Relapse remains the major cause of mortality after hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research has suggested that reducing the intensity of calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis may be an effective strategy for abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that the benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD. We conducted a study of risk factors for GVHD, to risk-stratify patients based on age. Patients age <18 years with leukemia who received myeloablative, T cell-replete MSD bone marrow transplantation and calcineurin inhibitor-based GVHD prophylaxis between 2000 and 2013 and were entered into the Center for International Blood and Marrow Transplant Research registry were included. The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 19%, that of grade II-IV aGVHD 7%, and that of chronic GVHD (cGVHD) was 16%. Compared with age 13 to 18 years, age 2 to 12 years was associated with a lower risk of grade II-IV aGVHD (hazard ratio [HR],.42; 95% confidence interval [CI],.26 to.70; P =.0008), grade II-IV aGVHD (HR,.24; 95% CI,.10 to.56; P =.001), and cGVHD (HR,.32; 95% CI,.19 to.54; P <.001). Compared with 2000-2004, the risk of grade II-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR,.36; 95% CI,.20 to.65; P =.0007) and in 2009-2013 (HR,.24; 95% CI..11 to.53; P =.0004). Similarly, the risk of grade III-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR,.23; 95% CI,.08 to.65; P =.0056) and 2009-2013 (HR,.16; 95% CI,.04 to.67; P =.0126) compared with those doing so in 2000-2004. We conclude that aGVHD rates have decreased significantly over time, and that children age 2 to 12 years are at very low risk for aGVHD and cGVHD. These results should be validated in an independent analysis, because these patients with high-risk malignancies may be good candidates for trials of reduced GVHD prophylaxis.
by
Evgeny Klyuchnikov;
Ulrike Bacher;
Nicolaus M. Kroeger;
Parameswaran N. Hari;
Kwang Woo Ahn;
Jeanette Carreras;
Veronika Bachanova;
Asad Bashey;
Jonathon Cohen;
Anita D'Souza;
César O. Freytes;
Robert Peter Gale;
Siddhartha Ganguly;
Mark S. Hertzberg;
Leona A. Holmberg;
Mohamed A. Kharfan-Dabaja;
Andreas Klein;
Grace H. Ku;
Ginna G. Laport;
Hillard M. Lazarus;
Alan M. Miller;
Alberto Mussetti;
Richard F. Olsson;
Shimon Slavin;
Saad Z. Usmani;
Ravi Vij;
William A. Wood;
David G. Maloney;
Anna M. Sureda;
Sonali M. Smith;
Mehdi Hamadani
Purpose: Comparison of long-term outcomes in patients with refractory/relapsed grade 1-2 follicular lymphoma (FL) after allogeneic (allo-HCT) vs. autologous hematopoietic cell transplantation (auto-HCT) in the rituximab-era.
Methods: Adult patients with relapsed/refractory grade 1-2 FL undergoing 1st reduced-intensity allo-HCT or 1st autograft during 2000-2012 were evaluated.
Results: A total of 518 rituximab-treated patients were included. Allo-HCT patients were younger; more heavily pretreated, and more patients had advanced stage and chemoresistant disease. The 5-year adjusted probabilities, comparing auto- vs. allo-HCT groups for non-relapse mortality (NRM) were 5% vs. 26% (p<0.0001); relapse/progression: 54% vs. 20% (p<0.0001); progression-free survival (PFS): 41% vs. 58% (p<0.001) and overall survival (OS): 74% vs. 66% (p=0.05). Auto-HCT was associated with a higher risk of relapse/progression beyond 5 months post-HCT (RR=4.4; p<0.0001), and worse PFS (RR=2.9; p<0.0001) beyond 11 months post HCT. In the first 24 months post HCT, auto-HCT was associated with improved OS (RR=0.41; p<0.0001), but beyond 24 months with inferior OS (RR=2.2; p=0.006). A landmark analysis of patients alive and progression-free at 2-years post-HCT confirmed these observations, showing no difference in further NRM between both groups, but significantly higher risk of relapse/progression (RR=7.3; p<0.0001) and inferior PFS (RR=3.2; p<0.0001) and OS (RR=2.1; p=0.04) following auto-HCT. The 10-year cumulative incidence of second hematological malignancies following allo- and auto-HCT was 0% and 7%, respectively.
Conclusion: Auto- and RIC-allo-HCT as 1st transplantation approach can provide durable disease control in grade 1-2 FL patients. Continued disease relapse-risk following auto-HCT translates into improved PFS and OS following allo-HCT, in long-term survivors.
by
Eric J. Chow;
Lynnette Anderson;
K. Scott Baker;
Smita Bhatia;
Gregory M.T. Guilcher;
Jennifer T. Huang;
Wendy Pelletier;
Joanna L. Perkins;
Linda S. Rivard;
Tal Schechter;
Ami Jayant Shah;
Karla Dee Wilson;
Kenneth Wong;
Satkiran Grewal;
Saro Armenian;
Lillian Meacham;
Daniel A. Mulrooney;
Sharon Castellino
Hematopoietic cell transplantation (HCT) is an important curative treatment for children with high-risk hematologic malignancies, solid tumors, and, increasingly, nonmalignant diseases. Given improvements in care, there are a growing number of long-term survivors of pediatric HCT. Compared with childhood cancer survivors who did not undergo transplantation, HCT survivors have a substantially increased burden of serious chronic conditions and impairments involving virtually every organ system and overall quality of life. This likely reflects the joint contributions of pretransplantation treatment exposures and organ dysfunction, the transplantation conditioning regimen, and any post-transplantation graft-versus-host disease (GVHD). In response, the Children's Oncology Group (COG) has created long-term follow-up guidelines (www.survivorshipguidelines.org) for survivors of childhood, adolescent, and young adult cancer, including those who were treated with HCT. Guideline task forces, consisting of HCT specialis ts, other pediatric oncologists, radiation oncologists, organ-specific subspecialists, nurses, social workers, other health care professionals, and patient advocates systematically reviewed the literature with regards to late effects after childhood cancer and HCT since 2002, with the most recent review completed in 2013. For the most recent review cycle, over 800 articles from the medical literature relevant to childhood cancer and HCT survivorship were reviewed, including 586 original research articles. Provided herein is an organ system-based overview that emphasizes the most relevant COG recommendations (with accompanying evidence grade) for the long-term follow-up care of childhood HCT survivors (regardless of current age) based on a rigorous review of the available evidence. These recommendations cover both autologous and allogeneic HCT survivors, those who underwent transplantation for nonmalignant diseases, and those with a history of chronic GVHD.
by
Ivana N. Micallef;
Patrick J. Stiff;
Auayporn P. Nademanee;
Richard T. Maziarz;
Mitchell E. Horwitz;
Edward A. Stadtmauer;
Jonathan Kaufman;
John M. McCarty;
Rita Vargo;
Peter D. Cheverton;
Martin Struijs;
Brian Bolwell;
John F. DiPersio
The purpose of this report is to analyze long-term clinical outcomes of patients exposed to plerixafor plus granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization. This was a study of patients with non-Hodgkin lymphoma (NHL; n = 167) and multiple myeloma (MM; n = 163) who were enrolled in the long-term follow-up of 2 pivotal phase III studies (NCT00741325 and NCT00741780) of 240 µg/kg plerixafor plus 10 µg/kg G-CSF, or placebo plus 10 µg/kg G-CSF to mobilize and collect CD34 + cells for autologous hematopoietic stem cell transplantation. Overall survival (OS) and progression-free survival (PFS) were evaluated over a 5-year period following the first dose of plerixafor or placebo. The probability of OS was not significantly different in patients with NHL or MM treated with plerixafor or placebo (NHL: 64%; 95% confidence interval [CI], 56% to 71% versus 56%; 95% CI, 44% to 67%, respectively; MM: 64%; 95% CI, 54% to 72% versus 64%; 95% CI, 53% to 73%, respectively). In addition, there was no statistically significant difference in the probability of PFS over 5 years between treatment groups in patients with NHL (50%; 95% CI, 44% to 67% for plerixafor versus 43%; 95% CI, 31% to 54% for placebo) or those with MM (17%; 95% CI, 10% to 24% for plerixafor versus 30%; 95% CI, 21% to 40% for placebo). In this long-term follow-up study, the addition of plerixafor to G-CSF for stem cell mobilization did not affect 5-year survival in patients with NHL or patients with MM.
by
Mehdi Hamadani;
Wael Saber;
Kwang Woo Ahn;
Jeanette Carreras;
Mitchell S. Cairo;
Timothy S. Fenske;
Robert Peter Gale;
John Gibson;
Gregory A. Hale;
Parameswaran N. Hari;
Jack W. Hsu;
David J. Inwards;
Rammurti T. Kamble;
Anderas Klein;
Dipnarine Maharaj;
David I. Marks;
David A. Rizzieri;
Bipin N. Savani;
Harry C. Schouten;
Edmund K Waller;
Baldeep Wirk;
Hillard M. Lazarus
Patients with chemorefractory mantle cell lymphoma (MCL) have a poor prognosis. We used the Center for International Blood and Marrow Transplant Research database to study the outcome of 202 patients with refractory MCL who underwent allogeneic hematopoietic cell transplantation (allo-HCT) using either myeloablative (MA) or reduced-intensity/nonmyeloablative conditioning (RIC/NST), during 1998-2010. We analyzed nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS). Seventy-four patients (median age, 54 years) received MA, and 128 patients (median age, 59 years) received RIC/NST. Median follow-up after allo-HCT was 35 months in the MA group and 43 months in the RIC/NST group. At 3 years post-transplantation, no significant between-group differences were seen in terms of NRM (47% in MA versus 43% in RIC/NST; P = .68), relapse/progression (33% versus 32%; P = .89), PFS (20% versus 25%; P = .53), or OS (25% versus 30%; P = .45). Multivariate analysis also revealed no significant between-group differences in NRM, relapse, PFS, or OS; however, receipt of a bone marrow or T cell-depleted allograft was associated with an increased risk of NRM and inferior PFS and OS. Our data suggest that despite a refractory disease state, approximately 25% of patients with MCL can attain durable remission after allo-HCT, and conditioning regimen intensity does not influence outcome of allo-HCT.
by
Timothy S. Fenske;
Mehdi Hamadani;
Jonathon Cohen;
Luciano J. Costa;
Brad Kahl;
Andrew M. Evens;
Paul A. Hamlin;
Hillard M. Lazarus;
Effie Petersdorf;
Christopher Bredeson
Non-Hodgkin lymphoma (NHL) constitutes a collection of lymphoproliferative disorders with widely varying biological, histological, and clinical features. For the B cell NHLs, great progress has been made due to the addition of monoclonal antibodies and, more recently, other novel agents including B cell receptor signaling inhibitors, immunomodulatory agents, and proteasome inhibitors. Autologous hematopoietic cell transplantation (auto-HCT) offers the promise of cure or prolonged remission in some NHL patients. For some patients, however, auto-HCT may never be a viable option, whereas in others, the disease may progress despite auto-HCT. In those settings, allogeneic HCT (allo-HCT) offers the potential for cure. Over the past 10 to 15 years, considerable progress has been made in the implementation of allo-HCT, such that this approach now is a highly effective therapy for patients up to (and even beyond) age 75 years. Recent advances in conventional lymphoma therapy, peritransplantation supportive care, patient selection, and donor selection (including the use of alternative hematopoietic cell donors), has allowed broader application of allo-HCT to patients with NHL. As a result, an ever-increasing number of NHL patients over age 60 to 65 years stand to benefit from allo-HCT. In this review, we present data in support of the use of allo-HCT for patients with diffuse large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma. These histologies account for a large majority of allo-HCTs performed for patients over age 60 in the United States. Where possible, we highlight available data in older patients. This body of literature strongly supports the concept that allo-HCT should be offered to fit patients well beyond age 65 and, accordingly, that this treatment should be covered by their insurance carriers.
by
Partow Kebriaei;
Claudio Anasetti;
Mei-Jie Zhang;
Hai-Lin Wang;
Ibrahim Aldoss;
Marcos de Lima;
Hanna Khoury;
Brenda M. Sandmaier;
Mary M. Horowitz;
Andrew Artz;
Nelli Bejanyan;
Stefan Ciurea;
Hillard M. Lazarus;
Robert Peter Gale;
Mark Litzow;
Christopher Bredeson;
Matthew D. Seftel;
Michael A. Pulsipher;
Jaap-Jan Boelens;
Muna Qayed
Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (Bu) to decrease toxicity. This retrospective study analyzed TBI and Bu on outcomes of ALL patients 18–60 years old, in first or second complete remission (CR), undergoing HLA-compatible sibling, related, or unrelated donor HCT, who reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014. TBI plus etoposide (25%) or cyclophosphamide (75%) was used in 819 patients, and intravenous Bu plus fludarabine (41%), clofarabine (30%), cyclophosphamide (15%), or melphalan (13%) was used in 299 patients. Bu-containing regimens were analyzed together, since no significant differences for patient outcomes were noted between them. Bu patients were older, with better performance status; took longer to achieve first CR and receive HCT; were treated more recently; and were more likely to receive peripheral blood grafts, antithymocyte globulin, or tyrosine kinase inhibitors. With median follow-up of 3.6 years for Bu and 5.3 years for TBI, adjusted 3-year outcomes showed treatment-related mortality Bu 19% versus TBI 25% (P =.04); relapse Bu 37% versus TBI 28% (P =.007); disease-free survival (DFS) Bu 45% versus TBI 48% (P =.35); and overall survival (OS) Bu 57% versus TBI 53% (P =.35). In multivariate analysis, Bu patients had higher risk of relapse (relative risk, 1.46; 95% confidence interval, 1.15 to 1.85; P =.002) compared with TBI patients. Despite the higher relapse, Bu-containing conditioning led to similar OS and DFS following HCT for ALL.