Reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation with fludarabine and melphalan is associated with durable disease control in myelodysplastic syndrome

Nakamura, Ryotaro; Rodríguez, Roberto; Palmer, Joycelynne; Stein, Anthony S.; Naing, Aung; Tsai, Ni‐Chun; Chang, Karen L.; Slovak, Marilyn L.; Bhatia, Ravi; Spielberger, Ricardo; Kogut, Neil; Pullarkat, Vinod; Kirschbaum, Mark; Forman, Stephen J.; O’Donnell, Margaret

doi:10.1038/sj.bmt.1705801

Cited by 44 publications

(23 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nakamura et al reported that a RIC regimen of fludarabine and melphalan, followed by GVHD prophylaxis with sirolimus and tacrolimus, was associated with a 35% rate of aGVHD (grades II to IV), and approximately 70% risk of cGVHD, although NRM was only 10.5% at 2 years. At 2 years, only 21% of patients experienced relapse, resulting in OS of 75% [24]. Potter et al described the single-center experience fludarabine, busulfan, and alemtuzumab conditioning for patients with MDS.…”

Section: Discussionmentioning

confidence: 99%

Total Lymphoid Irradiation–Antithymocyte Globulin Conditioning and Allogeneic Transplantation for Patients with Myelodysplastic Syndromes and Myeloproliferative Neoplasms

Benjamin

Chhabra

Kohrt

et al. 2014

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

Allogeneic hematopoietic cell transplantation (allo HCT) is the only curative therapy for the myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), but treatment toxicity has been a barrier to its more widespread use. The nonmyeloablative regimen of total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) permits the establishment of donor hematopoiesis necessary for the graft-versus-malignancy effect and is protective against acute graft-versus-host disease (aGVHD), but it has minimal direct cytotoxicity against myeloid diseases. We explored the use of TLI-ATG conditioning to treat 61 patients with allo HCT for MDS (n = 32), therapy-related myeloid neoplasms (n = 15), MPN (n = 9), and chronic myelomonocytic leukemia (n = 5). The median age of all patients was 63 years (range, 50 to 73). The cumulative incidence of aGVHD grades II to IV was 14% (95% confidence interval [CI], 4% to 23%) and for grades III to IV, 4% (95% CI, 0 to 9%), and it did not differ between patients who received allografts from related or unrelated donors. The cumulative incidence of nonrelapse mortality (NRM) at 100 days, 12 months, and 36 months was 0%, 7%, and 11%. Overall survival and progression-free survival were 41% (95% CI, 29% to 53%) and 35% (95% CI, 23% to 48%), respectively. The safety and tolerability of TLI-ATG, as exemplified by its low NRM, provides a foundation for further risk-adapted or prophylactic interventions to prevent disease progression.

show abstract

Section: Discussionmentioning

confidence: 99%

Total Lymphoid Irradiation–Antithymocyte Globulin Conditioning and Allogeneic Transplantation for Patients with Myelodysplastic Syndromes and Myeloproliferative Neoplasms

Benjamin

Chhabra

Kohrt

et al. 2014

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

show abstract

“…There are few reports of reduced intensity-conditioning regimens that have evaluated only MDS patients, to assess risk of relapse. Nakamura et al 18 analyzed 43 patients with MDS, including 15 progressing to AML, who were given a fludarabine-melphalan regimen. Two-year OS, DFS, relapse and transplant-related mortality were 54, 51, 16 and 35%, respectively.…”

Section: Discussionmentioning

confidence: 99%

5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation

Field

Perkins

Huang

et al. 2009

Bone Marrow Transplant

120

View full text Add to dashboard Cite

Relapse remains a leading cause for treatment failure after hematopoietic cell transplantation (HCT) in patients with intermediate-or high-risk myelodysplastic syndrome (MDS). To discern the impact of 5-azacitine treatment pretransplant on the risk for relapse after HCT, we analyzed the post transplant outcomes of all 54 consecutive patients with MDS or chronic myelomonocytic leukemia who received HCT from HLA-compatible donors according to pretransplant 5-azacitidine exposure. Thirty patients received a median of four (1-7) cycles of 5-azacitidine, and 24 patients did not receive 5-azacitidine before HCT. The 1-year estimates of overall survival, relapse-free survival and cumulative incidence of relapse were 47, 41 and 20%, for 5-azacitidine patients and 60, 51 and 32%, respectively, for non-5-azacytidine patients. These observations suggest that outcomes are similar in both groups with a trend toward decreased early relapse in patients receiving 5-azacitidine. 5-Azacitidine may be of value in stabilizing the disease, thereby allowing time for patients to reach transplant and does not appear to affect transplant outcomes.

show abstract

“…The incidences and severities of acute and chronic GvHD were in the range of those commonly reported for allogeneic HSCT using standard conditioning regimens. 5,8,30,32 Our GvHD prophylaxis regimen contained three doses of methotrexate. Using the other common version with four doses might have somewhat influenced the incidence of GvHD, but, on the other hand, also that of engraftment and possibly the occurrence of adverse effects.…”

Section: Discussionmentioning

confidence: 99%

Reduced-toxicity conditioning with treosulfan and fludarabine in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes: final results of an international prospective phase II trial

Ruutu¹,

Volin²,

Beelen³

et al. 2011

Haematologica

View full text Add to dashboard Cite

The online version of this article has a Supplementary Appendix. BackgroundAn alternative reduced-toxicity conditioning regimen for allogeneic transplantation, based on treosulfan and fludarabine, has recently been identified. The rationale for this study was to investigate the efficacy and safety of this regimen prospectively in patients with a primary myelodysplastic syndrome. Design and MethodsA total of 45 patients with primary myelodysplastic syndromes were conditioned with 3¥14 g/m² treosulfan and 5¥30 mg/m² fludarabine followed by allogeneic hematopoietic stem cell transplantation. Subtypes of myelodysplastic syndromes were refractory anemia with excess blasts-2 (44%), refractory cytopenia with multilineage dysplasia (27%), refractory anemia (9%), refractory anemia with ringed sideroblasts (4%), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (4%), refractory anemia with excess blasts-1 (2%), and myelodysplastic syndrome with isolated del (5q) (2%). The myelodysplastic syndrome was unclassified in 7% of the patients. Forty-seven percent of the patients had a favorable karyotype, 29% an unfavorable one, and 18% an intermediate karyotype. Patients were evaluated for engraftment, adverse events, graft-versus-host disease, non-relapse mortality, relapse incidence, overall survival and disease-free survival. ResultsAll but one patient showed primary engraftment of neutrophils after a median of 17 days. Nonhematologic adverse events of grade III-IV in severity included mainly infections and gastrointestinal symptoms (80% and 22% of the patients, respectively). Acute graft-versus-host disease grade II-IV developed in 24%, and extensive chronic graft-versus-host disease in 28% of the patients. After a median follow-up of 780 days, the 2-year overall and disease-free survival estimates were 71% and 67%, respectively. The 2-year cumulative incidences of non-relapse mortality and relapse were 17% and 16%, respectively. ConclusionsOur safety and efficacy data suggest that treosulfan-based conditioning therapy is a promising treatment option for patients with myelodysplastic syndromes. clinicaltrials.gov identifier: NCT01062490

show abstract

Reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation with fludarabine and melphalan is associated with durable disease control in myelodysplastic syndrome

Cited by 44 publications

References 31 publications

Total Lymphoid Irradiation–Antithymocyte Globulin Conditioning and Allogeneic Transplantation for Patients with Myelodysplastic Syndromes and Myeloproliferative Neoplasms

Total Lymphoid Irradiation–Antithymocyte Globulin Conditioning and Allogeneic Transplantation for Patients with Myelodysplastic Syndromes and Myeloproliferative Neoplasms

5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation

Reduced-toxicity conditioning with treosulfan and fludarabine in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes: final results of an international prospective phase II trial

Contact Info

Product

Resources

About