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Hill, B. T., Ahn, K. W., Hu, Z.-H., Aljurf, M., Beitinjaneh, A., Cahn, J.-Y., . . . Saber, W. (2018). Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia. Biology of blood and marrow transplantation, 24(3), 581-586
Open this publication in new window or tab >>Assessment of Impact of HLA Type on Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia
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2018 (English)In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 24, no 3, p. 581-586Article in journal (Refereed) Published
Abstract [en]

Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with many highly effective therapies. Chemorefractory disease, often characterized by deletion of chromosome 17p, has historically been associated with very poor outcomes, leading to the application of allogeneic hematopoietic stem cell transplantation (allo-HCT) for medically fit patients. Although the use of allo-HCT has declined since the introduction of novel targeted therapy for the treatment of CLL, there remains significant interest in understanding factors that may influence the efficacy of allo-HCT, the only known curative treatment for CLL. The potential benefit of transplantation is most likely due to the presence of alloreactive donor T cells that mediate the graft-versus-leukemia (GVL) effect. The recognition of potentially tumor-specific antigens in the context of class I and II major histocompatibility complex on malignant B lymphocytes by donor T cells may be influenced by subtle differences in the highly polymorphic HLA locus. Given previous reports of specific HLA alleles impacting the incidence of CLL and the clinical outcomes of allo-HCT for CLL, we sought to study the overall survival and progression-free survival of a large cohort of patients with CLL who underwent allo-HCT from fully HLA-matched related and unrelated donors at Center for International Blood and Marrow Transplant Research transplantation centers. We found no statistically significant association of allo-HCT outcomes in CLL based on previously reported HLA combinations. Additional study is needed to further define the immunologic features that portend a more favorable GVL effect after allo-HCT for CLL.

Keywords
CLL, HLA, Allogeneic transplantation
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-351084 (URN)10.1016/j.bbmt.2017.10.015 (DOI)000427663000023 ()29032274 (PubMedID)
Funder
NIH (National Institute of Health), U24 CA076518
Available from: 2018-05-18 Created: 2018-05-18 Last updated: 2018-05-18Bibliographically approved
Casulo, C., Friedberg, J. W., Ahn, K. W., Flowers, C., DiGilio, A., Smith, S. M., . . . Hamadani, M. (2018). Autologous Transplantation in Follicular Lymphoma with Early Therapy Failure: A National LymphoCare Study and Center for International Blood and Marrow Transplant Research Analysis. Biology of blood and marrow transplantation, 24(6), 1163-1171
Open this publication in new window or tab >>Autologous Transplantation in Follicular Lymphoma with Early Therapy Failure: A National LymphoCare Study and Center for International Blood and Marrow Transplant Research Analysis
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2018 (English)In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 24, no 6, p. 1163-1171Article in journal (Refereed) Published
Abstract [en]

Patients with follicular lymphoma (FL) experiencing early therapy failure (ETF) within 2 years of frontline chemoimmunotherapy have poor overall survival (OS). We analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) and the National LymphoCare Study (NLCS) to determine whether autologous hematopoietic cell transplant (autoHCT) can improve outcomes in this high-risk FL subgroup. ETF was defined as failure to achieve at least partial response after frontline chemoimmunotherapy or lymphoma progression within 2 years of frontline chemoimmunotherapy. We identified 2 groups: the non-autoHCT cohort (patients from the NLCS with ETF not undergoing autoHCT) and the autoHCT cohort (CIBMTR patients with ETF undergoing autoHCT). All patients received rituximab-based chemotherapy as frontline treatment; 174 non-autoHCT patients and 175 autoHCT patients were identified and analyzed. There was no difference in 5-year OS between the 2 groups (60% versus 67%, respectively; P = .16). A planned subgroup analysis showed that patients with ETF receiving autoHCT soon after treatment failure (≤1 year of ETF; n = 123) had higher 5-year OS than those without autoHCT (73% versus 60%, P = .05). On multivariate analysis, early use of autoHCT was associated with significantly reduced mortality (hazard ratio, .63; 95% confidence interval, .42 to .94; P = .02). Patients with FL experiencing ETF after frontline chemoimmunotherapy lack optimal therapy. We demonstrate improved OS when receiving autoHCT within 1 year of treatment failure. Results from this unique collaboration between the NLCS and CIBMTR support consideration of early consolidation with autoHCT in select FL patients experiencing ETF.

Keywords
Follicular lymphoma, Early therapy failure, Autologous transplantation, Early transplant, Rituximab, Chemoimmunotherapy
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-358199 (URN)10.1016/j.bbmt.2017.12.771 (DOI)000436056000009 ()29242111 (PubMedID)
Available from: 2018-08-31 Created: 2018-08-31 Last updated: 2018-08-31Bibliographically approved
Turcotte, L. M., Wang, T., Hemmer, M. T., Spellman, S. R., Arora, M., Couriel, D., . . . Verneris, M. R. (2018). Correspondence: Donor body mass index does not predict graft versus host disease following hematopoietic cell transplantation [Letter to the editor]. Bone Marrow Transplantation, 53(7), 932-937
Open this publication in new window or tab >>Correspondence: Donor body mass index does not predict graft versus host disease following hematopoietic cell transplantation
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2018 (English)In: Bone Marrow Transplantation, ISSN 0268-3369, E-ISSN 1476-5365, Vol. 53, no 7, p. 932-937Article in journal, Letter (Other academic) Published
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-365263 (URN)10.1038/s41409-018-0100-1 (DOI)000438311600021 ()29382954 (PubMedID)
Available from: 2018-11-12 Created: 2018-11-12 Last updated: 2018-11-12Bibliographically approved
Wood, W. A., Brazauskas, R., Hu, Z.-H., Abdel-Azim, H., Ahmed, I. A., Aljurf, M., . . . Saber, W. (2018). Country-Level Macroeconomic Indicators Predict Early Post-Allogeneic Hematopoietic Cell Transplantation Survival in Acute Lymphoblastic Leukemia: A CIBMTR Analysis. Biology of blood and marrow transplantation, 24(9), 1928-1935
Open this publication in new window or tab >>Country-Level Macroeconomic Indicators Predict Early Post-Allogeneic Hematopoietic Cell Transplantation Survival in Acute Lymphoblastic Leukemia: A CIBMTR Analysis
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2018 (English)In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 24, no 9, p. 1928-1935Article in journal (Refereed) Published
Abstract [en]

For patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic cell transplantation (alloHCT) offers a potential cure. Life-threatening complications can arise from alloHCT that require the application of sophisticated health care delivery. The impact of country-level economic conditions on post-transplantation outcomes is not known. Our objective was to assess whether these variables were associated with outcomes for patients transplanted for ALL. Using data from the Center for Blood and Marrow Transplant Research, we included 11,261 patients who received a first alloHCT for ALL from 303 centers across 38 countries between the years of 2005 and 2013. Cox regression models were constructed using the following macroeconomic indicators as main effects: Gross national income per capita, health expenditure per capita, and Human Development Index (HDI). The outcome was overall survival at 100 days following transplantation. In each model, transplants performed within lower resourced environments were associated with inferior overall survival. In the model with the HDI as the main effect, transplants performed in the lowest HDI quartile (n = 697) were associated with increased hazard for mortality (hazard ratio, 2.42; 95% confidence interval, 1.64 to 3.57; P < .001) in comparison with transplants performed in the countries with the highest HDI quartile. This translated into an 11% survival difference at 100 days (77% for lowest HDI quartile versus 88% for all other quartiles). Country-level macroeconomic indices were associated with lower survival at 100 days after alloHCT for ALL. The reasons for this disparity require further investigation.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2018
Keywords
Hematopoietic stem cell transplantation, Precursor cell lymphoblastic leukemia-lymphoma, Bone marrow, Health expenditures, Outcome assessment (Health care)
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-368766 (URN)10.1016/j.bbmt.2018.03.016 (DOI)000446644300026 ()29567340 (PubMedID)
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-10Bibliographically approved
Qayed, M., Wang, T., Hemmer, M. T., Spellman, S., Arora, M., Couriel, D., . . . Horan, J. (2018). Influence of Age on Acute and Chronic GVHD in Children Undergoing HLA-Identical Sibling Bone Marrow Transplantation for Acute Leukemia: Implications for Prophylaxis. Biology of blood and marrow transplantation, 24(3), 521-528
Open this publication in new window or tab >>Influence of Age on Acute and Chronic GVHD in Children Undergoing HLA-Identical Sibling Bone Marrow Transplantation for Acute Leukemia: Implications for Prophylaxis
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2018 (English)In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 24, no 3, p. 521-528Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
GVHD, Matched sibling donor transplantation, Children, Recipient age, Leukemia
National Category
Hematology Cancer and Oncology Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-351083 (URN)10.1016/j.bbmt.2017.11.004 (DOI)000427663000015 ()29155316 (PubMedID)
Funder
AstraZeneca
Available from: 2018-05-18 Created: 2018-05-18 Last updated: 2018-05-18Bibliographically approved
Myers, R. M., Hill, B. T., Shaw, B. E., Kim, S., Millard, H. R., Battiwalla, M., . . . Satwani, P. (2018). Long-Term Outcomes Among 2-Year Survivors of Autologous Hematopoietic Cell Transplantation for Hodgkin and Diffuse Large B-Cell Lymphoma. Cancer, 124(4), 816-825
Open this publication in new window or tab >>Long-Term Outcomes Among 2-Year Survivors of Autologous Hematopoietic Cell Transplantation for Hodgkin and Diffuse Large B-Cell Lymphoma
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2018 (English)In: Cancer, ISSN 0008-543X, E-ISSN 1097-0142, Vol. 124, no 4, p. 816-825Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Autologous hematopoietic cell transplantation (auto-HCT) is a standard therapy for relapsed classic Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL); however, long-term outcomes are not well described.

METHODS: This study analyzed survival, nonrelapse mortality, late effects, and subsequent malignant neoplasms (SMNs) in 1617 patients who survived progression-free for >= 2 years after auto-HCT for cHL or DLBCL between 1990 and 2008. The median age at auto-HCT was 40 years; the median follow-up was 10.6 years.

RESULTS: The 5-year overall survival rate was 90% (95% confidence interval [CI], 87%-92%) for patients with cHL and 89% (95% CI, 87%-91%) for patients with DLBCL. The risk of late mortality in comparison with the general population was 9.6-fold higher for patients with cHL (standardized mortality ratio [SMR], 9.6) and 3.4-fold higher for patients with DLBCL (SMR, 3.4). Relapse accounted for 44% of late deaths. At least 1 late effect was reported for 9% of the patients. A total of 105 SMNs were confirmed: 44 in the cHL group and 61 in the DLBCL group. According to a multivariate analysis, older age, male sex, a Karnofsky score < 90, total body irradiation (TBI) exposure, and a higher number of lines of chemotherapy before auto-HCT were risk factors for overall mortality in cHL. Risk factors in DLBCL were older age and TBI exposure. A subanalysis of 798 adolescent and young adult patients mirrored the outcomes of the overall study population.

CONCLUSIONS: Despite generally favorable outcomes, 2-year survivors of auto-HCT for cHL or DLBCL have an excess late-mortality risk in comparison with the general population and experience an assortment of late complications.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
autologous hematopoietic cell transplant, diffuse large B-cell lymphoma, Hodgkin lymphoma, late effects, nonrelapse mortality, survival
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-346657 (URN)10.1002/cncr.31114 (DOI)000424222600020 ()29125192 (PubMedID)
Available from: 2018-03-22 Created: 2018-03-22 Last updated: 2018-03-22Bibliographically approved
Chhabra, S., Ahn, K. W., Hu, Z.-H., Jain, S., Assal, A., Cerny, J., . . . Saber, W. (2018). Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia. BLOOD ADVANCES, 2(21), 2922-2936
Open this publication in new window or tab >>Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia
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2018 (English)In: BLOOD ADVANCES, ISSN 2473-9529, Vol. 2, no 21, p. 2922-2936Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-371540 (URN)10.1182/bloodadvances.2018024844 (DOI)000450684800012 ()30396912 (PubMedID)
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07Bibliographically approved
Bejanyan, N., Zhang, M.-J., Wang, H.-L., Lazaryan, A., de Lima, M., Marks, D. I., . . . Weisdorf, D. J. (2018). Pretransplant Consolidation Is Not Beneficial for Adults with ALL Undergoing Myeloablative Allogeneic Transplantation. Biology of blood and marrow transplantation, 24(5), 945-955
Open this publication in new window or tab >>Pretransplant Consolidation Is Not Beneficial for Adults with ALL Undergoing Myeloablative Allogeneic Transplantation
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2018 (English)In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 24, no 5, p. 945-955Article in journal (Refereed) Published
Abstract [en]

Allogeneic hematopoietic cell transplantation (alloHCT) is curative for patients with acute lymphoblastic leukemia (ALL) who achieve complete remission (CR1) with chemotherapy. However, the benefit of consolidation chemotherapy remains uncertain in patients undergoing alloHCT. We compared clinical outcomes of 524 adult patients with ALL in CR1 who received ≥2 (n = 109), 1 (n = 93), or 0 cycles (n = 322) of consolidation before myeloablative alloHCT from 2008 to 2012. As expected, time to alloHCT was longer with increasing cycles of consolidation. Patients receiving ≥2, 1, or 0 cycles of consolidation had an adjusted 3-year cumulative incidence of relapse of 20%, 27%, and 22%; 1-year transplant-related mortality (TRM) of 16%, 18%, and 23%; adjusted 3-year leukemia-free survival (LFS) of 54%, 48%, and 47%; and 3-year overall survival (OS) of 63%, 59%, and 54% (all P values >.40). Multivariable analysis confirmed that consolidation was not prognostic for LFS (relative risk, 1.20, 95% confidence interval, .86 to 1.67; P = .28 for no consolidation; RR, 1.18, 95% confidence interval, .79 to 1.76; P = .41 for 1 cycle versus ≥2 cycles = reference). Similarly, consolidation was not associated with OS, relapse, TRM, or graft-versus-host disease. We conclude that consolidation chemotherapy does not appear to provide added benefit in adult ALL patients with available donors who undergo myeloablative alloHCT in CR1.

Keywords
ALL, Consolidation chemotherapy, Myeloablative.conditioning, Allogeneic transplant
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-357580 (URN)10.1016/j.bbmt.2017.12.784 (DOI)000433400000010 ()29275139 (PubMedID)
Funder
AstraZeneca
Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-08-17Bibliographically approved
Radivoyevitch, T., Dean, R. M., Shaw, B. E., Brazauskas, R., Tecca, H. R., Molenaar, R. J., . . . Hashmi, S. K. (2018). Risk of acute myeloid leukemia and myelodysplastic syndrome after autotransplants for lymphomas and plasma cell myeloma. Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, 74, 130-136
Open this publication in new window or tab >>Risk of acute myeloid leukemia and myelodysplastic syndrome after autotransplants for lymphomas and plasma cell myeloma
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2018 (English)In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 74, p. 130-136Article in journal (Refereed) Published
Abstract [en]

Background: Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

Methods: 9028 recipients of hematopoietic cell autotransplants (1995-2010) for Hodgkin lymphoma (HL; n=916), non-Hodgkin lymphoma (NHL; n=3546) and plasma cell myeloma (PCM; n=4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS.

Results: 335 MDS/ AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR=4.0; 95% confidence interval [1.4, 11.6]) and NHL (HR=2.5 [1.1, 2.5]); (2) >= 3 versus 1 line of chemotherapy for NHL (HR=1.9 [1.3, 2.8]); and (3) subjects with NHL transplanted in 2005-2010 versus 1995-1999 (HR=2.1 [1.5, 3.1]). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/ MDS in HL, NHL and PCM to be 5-10 times the background rate. In contrast, relative risks were 10-50 for AML and approximately 100 for MDS in the autotransplant cohort.

Conclusions: There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.

Keywords
Autotransplant, AML, MDS, CIBMTR, SEER, Therapy-related, New cancers
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:uu:diva-369596 (URN)10.1016/j.leukres.2018.07.016 (DOI)000449112000021 ()30055822 (PubMedID)
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2018-12-19Bibliographically approved
Olsson, R. F. (2018). Self-Destructive Behavior among Full-Donor Blood and Marrow Grafts and the Association with Long-Term Graft Function. Biology of blood and marrow transplantation, 24(1), 1-2
Open this publication in new window or tab >>Self-Destructive Behavior among Full-Donor Blood and Marrow Grafts and the Association with Long-Term Graft Function
2018 (English)In: Biology of blood and marrow transplantation, ISSN 1083-8791, E-ISSN 1523-6536, Vol. 24, no 1, p. 1-2Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Hematology
Identifiers
urn:nbn:se:uu:diva-349319 (URN)10.1016/j.bbmt.2017.11.010 (DOI)000419933800001 ()29158078 (PubMedID)
Available from: 2018-05-02 Created: 2018-05-02 Last updated: 2018-05-02Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5970-2128

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