Prognostic factors for outcomes in allogeneic transplantation for CML in the imatinib era: a CIBMTR analysis

Khoury, H. Jean; Kukreja, Manisha; Goldman, John M.; Wang, Tao; Halter, Jörg; Arora, Mukta; Gupta, Vikas; Rizzieri, David A.; George, Biju; Keating, Armand; Gale, Robert Peter; Marks, David I.; McCarthy, Philip L.; Woolfrey, Ann E.; Szer, Jeffrey; Giralt, Sergío; Maziarz, Richard T.; Cortes, Jorge; Horowitz, Mary M.; Lee, Stephanie J.

doi:10.1038/bmt.2011.194

Cited by 87 publications

(62 citation statements)

References 19 publications

(19 reference statements)

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“…Potential clinical predictors included demographic characteristics, underlying disease, allogeneic stem cell source, donor status, conditioning regimen intensity (28), disease risk score (based on the 2014 American Society for Blood and Marrow Transplantation Request for Information Disease Classifications schema) (29), the HCT comorbidity index (HCTCI; a weighted score of pre-transplantation comorbidity) (30), and antibiotic use during the transplantation hospitalization. The examined pulmonary risk factors included history of smoking, chronic lung disease, abnormal baseline pulmonary function (impaired diffusing capacity of the…”

Section: Data Sources and Definitionsmentioning

confidence: 99%

Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation

Harris

Morjaria

Littmann

et al. 2016

Am J Respir Crit Care Med

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Rationale: Pulmonary complications (PCs) cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT). Shifts in gut microbiota have been linked to HCT outcomes; however, their effect on PCs is unknown.Objectives: To investigate whether changes in gut microbiota are associated with PCs after HCT.Methods: A single-center observational study was performed on 94 patients who underwent HCT from 2009 to 2011 and who were previously enrolled in a protocol for 16S ribosomal RNA sequencing of fecal microbiota. The primary endpoint, PC, was defined by new abnormal parenchymal findings on chest imaging in the setting of respiratory signs and/or symptoms. Outcomes were collected up to 40 months after transplant. Clinical and microbiota risk factors for PCs and mortality were evaluated using survival analysis.Measurements and Main Results: One hundred twelve PCs occurred in 66 (70.2%) subjects. A high comorbidity index (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.30-4.00; P = 0.004), fluoroquinolones (HR, 2.29, 95% CI, 1.32-3.98; P = 0.003), low baseline diversity (HR, 2.63; 95% CI, 1.22-5.32; P = 0.015), and g-proteobacteria domination of fecal microbiota (HR, 2.64; 95% CI, 1.10-5.65; P = 0.031), which included common respiratory pathogens, predicted PCs. In separate analyses, low baseline diversity was associated with PCs that occurred preengraftment (HR, 6.30; 95% CI, 1.42-31.80; P = 0.016), whereas g-proteobacteria domination predicted PCs postengraftment (HR, 3.68; 95% CI, 1.49-8.21; P = 0.006) and overall mortality (HR, 3.52; 95% CI, 1.28-9.21; P = 0.016). Postengraftment PCs were also independent predictors of death (HR, 2.50; 95% CI, 1.25-5.22; P = 0.009).Conclusions: This is the first study to demonstrate prospective changes in gut microbiota associated with PCs after HCT. Postengraftment PCs and g-proteobacteria domination were predictive of mortality. This suggests an adverse relationship between the graft and lung, which is perhaps mediated by bacterial composition in the gut. Further study is warranted.Keywords: stem cell transplantation; microbiota; pulmonary disease Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative therapy for many blood disorders and malignancies. Advances in transplant management have greatly improved outcomes (1). However, pulmonary complications (PCs) are associated with high morbidity and mortality. Although PCs have been reported in up to 70% of HCT recipients (2-4), the epidemiology is poorly defined in this heterogeneous population.Lung injury after HCT can occur early or late, present as acute or chronic, and involve one or more anatomic

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Section: Data Sources and Definitionsmentioning

confidence: 99%

Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation

Harris

Morjaria

Littmann

et al. 2016

Am J Respir Crit Care Med

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“…In the subgroup analysis of the CML phase IV study by Geman [22], the 5-year OS rate after HLA-matched related HSCT was approximately 40% in patients in AP. In recent report from the Center for International Blood and Marrow Transplant Research [23], the disease-free survival rate after allo-HSCT was 26%-27% in patients with AP-CML. The outcomes in the present cohort group, with 5-year OS, EFS, and PFS rates of 86.4%, 76.1%, and 78.1%, respectively, are better than those in the previous study.…”

Section: Discussionmentioning

confidence: 98%

Superiority of allogeneic hematopoietic stem cell transplantation to nilotinib and dasatinib for adult patients with chronic myelogenous leukemia in the accelerated phase

Zhu

et al. 2015

Front. Med.

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In the tyrosine kinase inhibitor (TKI) era, imatinib is the first-line therapy for patients with chronic myeloid leukemia (CML) in chronic or accelerated phase. Although second-generation TKIs (TKI2), including dasatinib and nilotinib, are appropriate treatment regimens for patients with disease that progressed to accelerated phase following imatinib therapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy. This study retrospectively analyzed the efficacy of TKI2 and HSCT for treatment of CML in accelerated phase. Ninety-three patients with CML registered in the Chinese CML alliance database from February 2001 to February 2014 were enrolled and divided into the TKI2 (n = 33) and allo-HSCT (n = 60) groups. In the TKI2 group, 26 and 7 patients received nilotinib and dasatinib, respectively, as initial TKI2 and 11 patients transferred to the alternative TKI2 after failure to one TKI2. In the allo-HSCT group, 22 (36.7%), 35 (58.3%), and 3 (10%) patients underwent allo-HSCT from an HLA-matched sibling donor, HLA mismatched/haploidentical donor, and unrelated donor, respectively. All patients in the HSCT group were engrafted. Overall, 69.7%, 48.5%, and 45.5% of patients presented hematological, cytogenetic, and major molecular responses, respectively, to at least one of TKI2. All 60 patients (100%) achieved CHR and cytogenetic response in the HSCT group. Patients in the TKI2 group exhibited lower 5-year overall survival rate (42.9% vs. 86.4%, P = 0.002), 5-year event-free survival rate (14.3% vs. 76.1%, P < 0.001), and 5-year progression-free survival (28.6% vs. 78.1%, P < 0.001) than those in the allo-HSCT group. Multivariate analysis showed that male sex and TKI2 therapy were predictors of poor overall survival, whereas hemoglobin < 100 g/L and TKI2 therapy were predictors of poor event-free survival and progression-free survival. These results indicated that allo-HSCT may be superior to nilotinib and dasatinib for adult patients with CML in accelerated phase.

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“…Of general importance to note, there are no indications that impact of transplant technology in CML differs from that in any other disease treated with HSCT [8,15,48]. …”

Section: Impact Of Hsct Methodologymentioning

confidence: 96%

The role of hematopoietic stem cell transplantation in chronic myeloid leukemia

2015

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Allogeneic hematopoietic stem cell transplantation (HSCT) is currently recommended as 2nd or 3rd line therapy for patients with chronic myeloid leukemia (CML) in first chronic phase or as salvage for patients with very advanced disease. As a consequence, numbers of HSCT in chronic phase have dropped significantly since the introduction of tyrosine kinase inhibitors (TKI), numbers of transplants in advanced disease to a lesser extent. These current recommendations consider primarily disease risk, defined as failure of TKI therapy; they might need to be adapted. We propose a more balanced appraisal of HSCT for individual patients which should include disease risk, transplant risk, and macroeconomic aspects. HSCT should be integrated into the treatment algorithms from diagnosis and be considered very early at first TKI failure for patients with high disease but low transplant risk. For patients with very advanced disease and high transplant risk in contrast, HSCT might only be recommended in a restricted research setting.

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Prognostic factors for outcomes in allogeneic transplantation for CML in the imatinib era: a CIBMTR analysis

Cited by 87 publications

References 19 publications

Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation

Gut Microbiota Predict Pulmonary Infiltrates after Allogeneic Hematopoietic Cell Transplantation

Superiority of allogeneic hematopoietic stem cell transplantation to nilotinib and dasatinib for adult patients with chronic myelogenous leukemia in the accelerated phase

The role of hematopoietic stem cell transplantation in chronic myeloid leukemia

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