Serious acute or chronic graft-versus-host disease after hematopoietic cell transplantation: a comparison of myeloablative and nonmyeloablative conditioning regimens

Sala‐Torra, Olga; Petřek, Martin; Storer, Barry E.; Traina, Fabı́ola; Sorror, Mohamed L.; Storb, Rainer; Sandmaier, Brenda M.; Flowers, Mary E.D.

doi:10.1038/sj.bmt.1705987

Cited by 17 publications

(10 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These rates compare favorably with reported rates of chronic GVHD following RIC transplantation of 33% to 78%. [1][2][3][12][13][14][38][39][40][41][42][43][44][45] Addition of ATG in standard RIC regimens may be associated with a reduction in rates of chronic GVHD, however, not all investigators have confirmed this finding. 10,35,44,45 The relatively low rate of chronic GVHD we observed may result, in part, from the low rate of acute GVHD, as acute GVHD is a significant risk factor for development of chronic GVHD.…”

Section: Tli and Atg For Transplantmentioning

confidence: 81%

TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors

Kohrt¹,

Turnbull

Heydari³

et al. 2009

Blood

152

166

View full text Add to dashboard Cite

A hematopoietic cell transplantation regimen was adapted from a preclinical model that used reduced-intensity conditioning (RIC) and protected against graft-versushost disease (GVHD) by skewing residual host T-cell subsets to favor regulatory natural killer T cells. One hundred eleven patients with lymphoid (64) and myeloid (47) malignancies received RIC using total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) followed by the infusion of granulocyte colony-stimulating factor-mobilized grafts. Included were 34 patients at least 60 years of age, 32 patients at high risk of lymphoma relapse after disease recurrence following prior autologous transplantation, and 51 patients at high risk of developing GVHD due to lack of a fully human leukocyte antigen (HLA)-matched related donor. Durable chimerism was achieved in 97% of patients. Cumulative probabilities of acute GVHD (grades II-IV) were 2 and 10% of patients receiving related and unrelated donor grafts. Nonrelapse mortality (NRM) at 1 year was less than 4%. Cumulative incidence of chronic GVHD was 27%. The 36-month probability of overall and eventfree survival was 60% and 40%, respectively. Disease status at start of conditioning and the level of chimerism achieved after transplantation significantly impacted clinical outcome. The high incidence of sustained remission among patients with active disease at time of transplantation suggests retained graftversus-tumor reactions. Active trial registration currently at clinicaltrials.gov un-

show abstract

Section: Tli and Atg For Transplantmentioning

confidence: 81%

TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors

Kohrt¹,

Turnbull

Heydari³

et al. 2009

Blood

152

166

View full text Add to dashboard Cite

show abstract

“…All allogeneic transplant recipients received prophylaxis for acute GVHD depending on the type of donor and protocol in use at time of HCT and generally included either methotrexate or methotrexate and a calcineurin inhibitor [29–31]. Acute and chronic GVHD were diagnosed, graded, and treated as previously described [32–35]. Hepatitis C virus (HCV) screening began in 1991 as previously described [36].…”

Section: Methodsmentioning

confidence: 99%

Hypertension in Long-Term Survivors of Pediatric Hematopoietic Cell Transplantation

Hoffmeister

Hingorani

Storer

et al. 2010

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

A retrospective study was conducted to determine risk factors for the development of hypertension (HTN) and to describe the prevalence among long-term survivors of pediatric hematopoietic cell transplant (HCT). Records of 689 pediatric patients who survived 5 years or more after HCT from 1969–2004 were reviewed for development of HTN. In children, HTN was defined as either a systolic or diastolic pressure ≥95th percentile according to age, gender, and height. In adults, HTN was defined as systolic pressures ≥140 mmHg and/or diastolic pressures ≥90 mmHg in non-diabetic adults and systolic pressures ≥130 and/or diastolic pressures ≥80 in diabetic adults. Multivariate Cox regression models were used to estimate the hazard ratio (HR) of risk factors associated with HTN. All patients included were off immunosuppressive therapy. Patients had been treated with total body irradiation (TBI) (n=482, 70%) or non-TBI regimens (n=207, 30%) followed by autologous (n=87), related (n=484), or unrelated donor HCT (n=118). Median follow-up was 16 (range, 5–36) years. HTN developed in 120 patients with a 30-year cumulative incidence of 36%. Risk factors associated with HTN were acute kidney injury (doubling of baseline creatinine by day 100 after HCT) (HR=2.5; 95% confidence interval (CI) 1.7–3.7, p <0.0001), TBI in the preparative regimen (HR=2.1; 95% CI 1.3–3.3, p = 0.001), donor type (autologous HR=2.4; 95% CI 1.3–4.4 and unrelated donor HR=1.8; 95% CI 1.0–3.2, p = 0.01), obesity (HR=4.0; 95% CI 2.3–6.8, p <0.0001), diabetes (HR=6.7; 95% CI 3.9–11.0, p <0.0001), and history of growth hormone therapy (HR=1.6; 95% CI 1.0–2.5, p = 0.05). Patients with a positive history of hepatitis C infection were less likely to develop HTN (HR=0.5; 95% CI 0.3–0.9, p = 0.009). Prevalence of HTN was 15% overall and among survivors 11–17 and 18–39 years old, the prevalence was 10% and 14% or triple and double that of the general U.S. population, respectively. Pediatric HCT survivors are more likely to develop HTN than the general population and should be monitored for HTN throughout adulthood.

show abstract

“…This rate was comparable with what was observed in patients with a variety of hematologic malignancies who received the same nonmyeloablative HCT conditioning. 42 Long-term systemic therapy was needed to control GVHD over time, with 25% of current patients reported to still be on immunosuppression 7 years after allografting. In this study, we were not able to associate clinical GVHD with protection from relapse.…”

Section: Discussionmentioning

confidence: 99%

Long-term outcome of patients with multiple myeloma after autologous hematopoietic cell transplantation and nonmyeloablative allografting

Rotta

Storer

Sahebi

et al. 2009

Blood

104

View full text Add to dashboard Cite

Autologous hematopoietic cell transplantation (HCT) followed by nonmyeloablative allogeneic HCT (auto/alloHCT) provides cytoreduction and graft-versus-myeloma effects. We report on long-term outcomes of 102 patients with multiple myeloma who received auto/alloHCT with a median follow-up of 6.3 years. Treatment consisted of high-dose melphalan and autograft followed by 2-Gy total body irradiation, with or without fludarabine, and alloHCT from human leukocyte antigen-identical siblings. Postgrafting immunosuppressive agent was cyclosporine or tacrolimus and mycophenolate mofetil. Forty-two percent of patients developed grade 2 to 4 acute graft-versushost disease (GVHD) and 74% extensive chronic GVHD. Five-year nonrelapse mortality after allografting was 18%, 95% related to GVHD or infections. Among 95 patients with detectable disease, 59 achieved complete remissions. Median time to progression was 5 years. Median overall survival (OS) was not reached. Median progression-free survival (PFS) was 3 years. Five-year OS and PFS were 64% and 36%, respectively. Seventy-three patients receiving autoHCT within 10 months from treatment initiation had 5-year OS of 69% and PFS of 37%. In multivariate analysis, ␤-2-microglobulin of more than 3.5 g/mL at diagnosis and auto/ alloHCT more than 10 months after treatment initiation correlated with shorter OS (P ‫؍‬ .03 and P ‫؍‬ .02) and PFS (P ‫؍‬ .04 and P ‫؍‬ .03), whereas Karnofsky scores less than 90% at allotransplantation correlated with shorter PFS only (P ‫؍‬ .005). Long-term disease control and GVHD remain key issues. (Blood. 2009;113:3383-3391)

show abstract

Serious acute or chronic graft-versus-host disease after hematopoietic cell transplantation: a comparison of myeloablative and nonmyeloablative conditioning regimens

Cited by 17 publications

References 37 publications

TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors

TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors

Hypertension in Long-Term Survivors of Pediatric Hematopoietic Cell Transplantation

Long-term outcome of patients with multiple myeloma after autologous hematopoietic cell transplantation and nonmyeloablative allografting

Contact Info

Product

Resources

About