scholarly journals Allogeneic Stem Cell Transplantation With Reduced Intensity Conditioning As Treatment For Mature T-Cell Lymphomas

2010 ◽  
Vol 16 (2) ◽  
pp. S238
Author(s):  
M.L. Delioukina ◽  
J. Palmer ◽  
J.M. Zain ◽  
N. Tsai ◽  
S. Forman
Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2224-2224
Author(s):  
Hubertus C. Buyck ◽  
Samantha J. Paston ◽  
Mark W. Lowdell ◽  
Stephen Mackinnon ◽  
Vincent C. Emery

Abstract CMV reactivation after allogeneic stem cell transplantation remains problematic and is increasing in frequency with the use of reduced intensity conditioning regimens. A functional immune response is critical to control viral replication and hence disease. In this study, 19 allogeneic stem cell transplant recipients at risk for CMV reactivation were followed for a median of 185 days. Six patients received myeloablative conditioning and thirteen patients received reduced intensity conditioning therapy. Functional CMV specific immune responses were monitored by flow cytometry, measuring CD4 and CD8 specific intracellular interferon gamma production in response to stimulation with peptide pools of 15 mer overlapping peptides spanning the entire length of the immunodominant PP65 and IE1 proteins. In addition the CD4 response to whole CMV antigen, which is capable of presenting multiple viral antigens, was also determined. 53% of patients experienced a CMV reactivation with a median time to 1st reactivation of 53.5 days (range 20–134). In comparison with the CMV reactivation group, the mean day 50 CD4 whole CMV antigen response was approximately 2 logs lower in the reactivated group (0.065X106/L) than the non-reactivated group (3.620X106/L) suggesting that CMV specific CD4 function is an important predictor of patients at risk of CMV reactivation. The incidence of CMV reactivation in patients receiving Campath-1H was 71% (10 out of 14 patients) while none of the 5 patients in the non-Campath-1H group reactivated. The use of Campath-1H as part of the conditioning regimen was associated with a significantly lower day 50 CD4 whole CMV antigen response (0.06X106/L) vs (4.53X106/L) for the non-Campath-1H group, suggesting a mechanism for the observed increased frequency of CMV reactivation with the use of this agent. The relative contribution of the CD4 and CD8 responses to IE1 and PP65 has also been determined in this patient group. In summary, the absolute functional helper T cell response to CMV was predictive of viral reactivation following transplant.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5863-5863
Author(s):  
Sara Lozano ◽  
Amaya Zabalza ◽  
Intza Aoiz ◽  
Mohamed Hamdi Djatri ◽  
Pedro Arregui ◽  
...  

Abstract Background: In vivo T-cell depletion with Alemtuzumab reduces the incidence of acute and chronic graft-versus-host disease (GvHD) and graft failure, yet it results in an increase of opportunistic infections and delayed immune recovery. In addition, Alemtuzumab has considerable anti-lymphoma activity in T-cell neoplasms. We report on a pilot study analysing the safety and feasibility of Alemtuzumab as pre-conditioning prior to reduced intensity conditioning allogeneic stem cell transplantation (RIC-alloSCT) in patients diagnosed with T-cell non-Hodgkin lymphoma. Methods: Six consecutive patients diagnosed with a T-cell lymphoid malignancy underwent RIC-alloSCT from a HLA-identical sibling (n=5) or a matched unrelated donor (n=1). Diagnosis were Angioimmunoblastic T-cell lymphoma (n=3), hepato-splenic gamma-delta T-cell lymphoma (n=1), T/NK cavum lymphoma (n=2) and Sèzary Syndrome (n=1). All received unmanipulated peripheral blood stem cells; At transplantation 2 patients were in CR, and 4 in PR. Median number of prior regimens was 2 (range 2-5). Conditioning regimen included Fludarabine (5 x 30mg/m2) and Melphalan (2 x 70mg/m2) in all cases. GvHD prophylaxis comprised Cyclosporine A and Methotrexate. The pre-conditioning protocol consisted on 6 escalating doses of intravenous Alemtuzumab starting on day -28 (3 mg on day -28, 10 mg on day -26 followed by four doses of 30 mg on days -24 to -17) given 3 times a week (MWF) on an out-patient basis. Results: Five patients received all six doses of Alemtuzumab as planned whereas one patient received only four doses for logistic reasons related to donor availability. Acetaminophen, Hydrocortisone and Dexchlorpheniramine were administered as pre-medication in all cases with no severe infusional reaction observed. There were no delays in proceeding to SCT conditioning and patients develop no infectious complications during the Alemtuzumab - alloSCT interval. All patients engrafted with a median time to neutrophil engraftment of 23 days (range 14-27). Acute skin GvHD (grade I and III) was observed in 2 patients (33.3%), both obtaining a CR with topical and systemic corticosteroids respectively. Two patients developed mild ocular chronic GvHD (one after subsequent infusions of donor lymphocytes - DLI) but none has suffered from extensive chronic GvHD. No opportunistic infection was observed apart from CMV reactivation that developed in 3 out of 4 seropositive patients (no CMV disease was observed). All patients experienced delayed immune reconstitution (CD4 >200/ul) at a median of 321 days (range 229-518). All 4 patients in PR prior to alloSCT achieved a complete remission. Only one patient (diagnosed with Sèzary Syndrome) experienced a relapsed and responded to DLI. With a median follow-up of 42 months, all patients remain alive and in CR. Conclusions: Our preliminary results suggest that administration of Alemtuzumab prior to reduced intensity conditioning is feasible and safe. In addition to providing T-cell depletion, Alemtuzumab may improve the response rate in T-cell lymphoid malignancies without increasing the risk of infectious complications. These results require further validation in larger phase II studies. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


Sign in / Sign up

Export Citation Format

Share Document