Prediction and Prevention of Transplant Related Mortality from Pulmonary Causes Following Total Body Irradiation and Allogeneic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1836-1836 ◽  
Author(s):  
Bipin Savani ◽  
Aldemar Montero ◽  
Bernadette Gochiuo ◽  
Nene Nlonda ◽  
Richard Childs ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pulmonary Function ◽  
Median Time ◽  
Total Body Irradiation ◽  
Pulmonary Function Tests ◽  
Diffusion Capacity ◽  
Function Tests ◽  
Conditioning Regimens ◽  
Total Body ◽  
Related Mortality

Abstract Between 7/1997 and 8/2004, 146 consecutive patients with hematological malignancies received a T cell depleted peripheral blood stem cell transplant (PBSCT) from an HLA identical sibling using three successive conditioning regimens: (A): 13.6Gy total body irradiation (TBI) + cyclophosphamide 120mg/kg (Cy) (n=85) , (B) 12.0Gy TBI with lung shielding to 9.0 Gy + Cy + fludarabine 125mg/m2 (Flu) , n= 35, (C) 12.0Gy TBI with lung shielding to 6.0 Gy + Cy + Flu, n= 26. Ninety-four (65.4%) had standard risk disease (transplant in first complete remission of acute leukemia, CML in chronic phase, and MDS-RA); the remainder had more advanced disease or unfavorable diagnoses. Actuarial transplant related mortality (TRM) was 16.4 ± 3%, at a median time of 103 days (range 23–238). Of the 21 transplant related deaths 14 (67%) were from pulmonary causes (6, idiopathic interstitial pneumonia (IP), 4 acute respiratory distress syndrome (ARDS), and pneumonia from CMV (2), RSV (1) and bacterial origin (1). Median time to death from IP and ARDS was 71 and 66 days post-transplant respectively. Kaplan-Meier analysis was used to study factors affecting pulmonary TRM. Pre-transplant characteristics predictive for pulmonary-related TRM are shown in the table. Patients with high risk disease and CML patients who had received busulfan for more than one month were at significantly greater risk of developing both pulmonary TRM and IP. Patients who smoked were significantly more at risk to develop ARDS and fatal pulmonary infection. Pre-transplant pulmonary function tests were highly predictive for pulmonary TRM. Diffusion capacity of the lung for carbon monoxide (DLCO), vital capacity and FEV-1 were highly correlated, but the most predictive parameter was DLCO: Of 48 patients with <85% normal vs. 98 with >85% of normal diffusion capacity, 6 vs 0 had IP, p<0.001, 4 vs 0 had ARDS, p=0.01 and 11 vs 3 had pulmonary TRM, p=0.0003. The death from all pulmonary causes was highest in protocol A (no lung shielding) and significantly less in conditioning regimens B+C (lung shielding) (12/85 vs 2/61 deaths, p = 0.05). These results indicate that after TBI and PBSCT, pulmonary causes contribute significantly to TRM, but can be predicted by patient characteristics and pulmonary function tests and may be reduced by lung shielding.

Pretreatment pulmonary function tests predict risk of mortality following fractionated total body irradiation without lung dose reduction prior to stem cell transplant

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6550-6550
Author(s):  
J. R. Mansueti ◽  
A. K. Singh ◽  
S. E. Karimpour ◽  
P. Guion ◽  
H. Ning ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pulmonary Function ◽  
Dose Reduction ◽  
Total Body Irradiation ◽  
Stem Cell Transplant ◽  
Pulmonary Function Tests ◽  
Cell Transplant ◽  
Lung Dose ◽  
Diffusion Capacity ◽  
Total Body

6550 Background: Peripheral blood stem cell transplantation (PBSCT) is a key component in the treatment of various malignancies. Preparatory regimens for PBSCT often include total body irradiation (TBI). Pulmonary toxicity is often prominent, and is felt to be related to total lung dose and dose rate. The Radiation Oncology Branch of the National Institute of Health initially administered TBI without lung shielding, however shielding was added in 2002. Pulmonary function testing (PFT) was undertaken both before and after stem cell transplant and TBI for all patients. The PFT results were analysed to test the hypothesis that TBI patients with pre-treatment combined ventilation/diffusion capacity deficits, defined as both FEV1 and DLCO below 100% predicted, would benefit most from reduction of lung dose. Methods: From 1997–2004, 146 consecutive patients with hematologic malignancies received fractionated TBI before PBSCT. The first 85 patients were treated without lung dose reduction to 13.6 Gray (Gy). Thereafter, total body dose was decreased to 12 Gy (1.5 Gy BID for 4 days). Initially, lung dose was limited to 9 Gy by use of lung shielding. Later lung dose was reduced to 6 Gy. All patients received PFTs prior to treatment, 90 days after treatment, and annually. Results: Median F/U was 44 months (range 12–90 months). Sixty-one patients had combined ventilation/diffusion capacity deficits defined as both a forced expiratory volume in the first second (FEV1) and a diffusion capacity of carbon dioxide (DLCO) less than 100% predicted. Of these 61, 27 had lung dose reduction and 34 did not. One-year survival was 71% versus 50% with and without lung dose reduction respectively (log rank test p=0.042). Eighty-five patients had FEV1 and/or DLCO greater than or equal to 100% predicted; 34 were treated with lung dose reduction and 51 without. In both groups, 1 year survival was 70%. Conclusions: Among patients treated without lung dose reduction, survival was significantly worse among those with pretreatment combined ventilation/diffusion capacity deficits. Among those with combined ventilation/diffusion capacity deficits, lung dose reduction significantly improved survival. No significant financial relationships to disclose.

ISOLATED ABNORMALITIES OF DIFFUSION CAPACITY (DLCO) IN PULMONARY FUNCTION TESTS AMONG INNER CITY PATIENTS

CHEST Journal ◽  
2008 ◽  
Vol 134 (4) ◽  
pp. 49S
Author(s):  
Ibrahim H. Abou Daya ◽  
Muhammad U. Anwer ◽  
Gilda Diaz-Fuentes ◽  
Steve Blum ◽  
Latha Menon
Keyword(s):  
Pulmonary Function ◽  
Inner City ◽  
Pulmonary Function Tests ◽  
Diffusion Capacity ◽  
Function Tests

Pulmonary Graft-Versus-Host Disease After Reduced Toxicity Conditioning with Fludarabin, Carmustine and Melphalan Prior to Hematopoietic Stem Cell Transplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1266-1266
Author(s):  
Jesus Duque-Afonso ◽  
Antje Prasse ◽  
Ralph Wäsch ◽  
Hartmut Bertz ◽  
Jurgen Finke ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Pulmonary Function ◽  
Pulmonary Function Tests ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Function Tests ◽  
Gvhd Prophylaxis ◽  
Reduced Toxicity

Abstract Abstract 1266 Allogeneic hematopoietic stem cell transplantation (HSCT) of older or comorbid patients has become feasible due to new protocols for reduced toxicity/intensity conditioning. Particularly using fludarabine, BCNU and melphalan (FBM) as preparative regimen confers reduced toxicity with substantial anti-leukemic activity. Nevertheless, chronic Graft-versus-Host disease (cGvHD) of the lung remains a serious non infectious, late onset pulmonary complication, contributing to treatment related morbidity and mortality. Since the clinical entity of pulmonary cGvHD after reduced toxicity/intensity conditioning has not yet been well characterized, we performed a retrospective analysis of patients, who were transplanted after FBM conditioning at the University Hospital Freiburg between 1998 and 2007, were alive at least 100 days after HSCT and have pulmonary function tests available. 259 patients were enrolled in this study (median age at PBSCT of 61 years (range 24–76)) with a median follow up of 33 months (range 4–133). All patients received conditioning with fludarabin (4-5 × 30 mg/m2), BCNU (or carmustin, patients> 55 years: 2×150 mg/m2, <55 years: 2×200 mg/m2) and melphalan (patients >55 years 1×110mg/m2, <55 years: 1×140 mg/m2, fo). Peripheral stem cell grafts were used in most of the cases together with cyclosporin based GvHD prophylaxis. 27 patients (10.4 %) developed a pulmonary cGvHD as defined by NIH criteria with a median time after HSCT of 13 months (range 4–102). In those patients, pulmonary function tests 6 months after HSCT revealed a significant reduction in mean % of predicted value in FEV1 (88 v. 79 %), MEF50 (63 v. 49 %) and the ratio of FEV1/FVC (80 v. 75 %), as early predictive parameters for developing pulmonary GvHD. However, no differences in pulmonary function tests were found predictive for developing pulmonary GvHD at the time of HSCT. The patients with pulmonary GvHD showed at the time of diagnosis in comparison to values before HSCT a reduction in % of predicted FEV1 (85 v. 57 %), of predicted VCmax (84 v. 71 %) and an increase of the ratio of RV/TLC (39 v. 49 %). In cumulative incidence curves, we found significant differences in decrease >10 % of the initial value of FEV1, in ratio of RV/TLC >45 %, in values of MEF50 <25% and MEF25 <25% of predicted value. In the multivariate analysis, following risk factors were associated with developing pulmonary cGvHD: age less than 55 years at HSCT, chronic GvHD, GvHD prophylaxis with in vivo anti T cell antibodies and lung disease (e.g. infections) after HSCT. Patients with pulmonary GvHD had a statistically significant longer disease free survival and overall survival and less relapse incidence. In conclusion, we found several risk factors and changes in pulmonary function tests associated with developing pulmonary GvHD in HSCT after conditioning with a reduced toxicity protocol (FBM) in the largest cohort of patients investigated so far. These findings might help to identify a risk population after reduced intensity conditioning and therefore result in personalized measures for GvHD prophylaxis and therapy. Disclosures: No relevant conflicts of interest to declare.

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