Haploidentical stem cell transplantation after a reduced-intensity conditioning regimen for the treatment of advanced hematologic malignancies: posttransplantation CD8-depleted donor lymphocyte infusions contribute to improve T-cell recovery

Dodero, Anna; Carniti, Cristiana; Raganato, Anna; Vendramin, Antonio; Farina, Lucia; Spina, Francesco; Carlo‐Stella, Carmelo; Terlizzi, Simona Di; Milanesi, Marco; Longoni, Paolo; Gandola, Lorenza; Lombardo, Claudia; Corradini, Paolo

doi:10.1182/blood-2008-10-183723

Cited by 69 publications

(48 citation statements)

References 27 publications

(30 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The reduction of the DLI dose might lead to a reduced induction of GVHD, as has been recently shown for the early prophylactic application of CD8 depl DLI in the haploidentical setting. 17 In addition, the design of our clinical trial included a DLI dose escalation, and occurrence of GVHD was the major stopping criteria. Therefore, a higher rate of GVHD was inherent to the protocol.…”

Section: Resultsmentioning

confidence: 99%

Donor CD4 T cells convert mixed to full donor T-cell chimerism and replenish the CD52-positive T-cell pool after alemtuzumab-based T-cell-depleted allo-transplantation

Meyer

Wagner

Konur

et al. 2009

Bone Marrow Transplant

View full text Add to dashboard Cite

Donor lymphocyte infusions (DLI) are used to resolve mixed T-cell chimerism (TCC) after allo-SCT despite a substantial risk of GVHD. We analyzed the impact of prophylactic CD8-depleted (CD8 depl ) DLI in 20 recipients of anti-CD52 alemtuzumab in vivo T-cell-depleted allografts with declining donor TCC after day þ 60. A total of 13 patients received CD8 depl DLI and 7 patients did not. All but one of the DLI patients converted to complete donor T-cell chimeras, whereas only one non-DLI patient converted spontaneously. DLI induced transient acute GVHD in five and extensive chronic GVHD in two patients. These data suggest the use of CD8 depl DLI as an effective treatment for mixed TCC, particularly in patients at high risk for GVHD. We also observed that the majority of reconstituting donor-derived T cells after alemtuzumab conditioning were CD52-negative. CD8 depl DLI significantly increased the proportion of CD52-positive CD4 T cells, whereby their beneficial effect on reconstituting the post-transplant T-cell repertoire was shown.

show abstract

Section: Resultsmentioning

confidence: 99%

Donor CD4 T cells convert mixed to full donor T-cell chimerism and replenish the CD52-positive T-cell pool after alemtuzumab-based T-cell-depleted allo-transplantation

Meyer

Wagner

Konur

et al. 2009

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…12 Those patients did not receive any GVHD prophylaxis. Acute GVHD was defined on the basis of the criteria published by Glucksberg et al, and chronic GVHD was classified as limited or extensive on the basis of the criteria of Sullivan et al 13,14 Staging Procedure and FDG-PET Imaging Disease status before and after alloSCT was assessed by means of a physical examination, blood chemistry, contrast-enhanced CT, bone marrow biopsy (when clinically indicated), and FDG-PET imaging (FDG-PET/CT from 2004 onward).…”

Section: Original Article 5002mentioning

confidence: 99%

Pretransplantation [18‐F]fluorodeoxyglucose positron emission tomography scan predicts outcome in patients with recurrent Hodgkin lymphoma or aggressive non‐Hodgkin lymphoma undergoing reduced‐intensity conditioning followed by allogeneic stem cell transplantation

Dodero

Crocchiolo

Miceli

et al. 2010

Cancer

Self Cite

View full text Add to dashboard Cite

BACKGROUND:The use of positron emission tomography (PET) scanning in Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphoma (HG-NHL) has recognized prognostic value in patients who are receiving chemotherapy or undergoing autologous stem cell transplantation (SCT). In contrast, the role of PET before reduced-intensity conditioning (RIC) and followed by allogeneic SCT has not been investigated to date. METHODS: PET was used to assess 80 patients who had chemosensitive disease (34 patients with HG-NHL and 46 patients with HL) before they underwent allogeneic SCT: 42 patients had negative PET studies, and 38 patients had positive PET studies. Patients underwent allograft from matched related siblings (n ¼ 41) or alternative donors (n ¼ 39). RESULTS: At the time of the last follow-up, 48 patients were alive (60%), and 32 had died. The 3-year cumulative incidence of nonrecurrence mortality and disease recurrence was 17% and 40%, respectively. The cumulative incidence of disease recurrence was significantly lower in the PET-negative patients (25% vs 56%; P ¼ .007), but there was no significant difference between the patients with or without chronic graft-versus-host disease (P ¼ .400). The patients who had negative PET studies before undergoing allogenic SCT also had significantly better outcomes in terms of 3-year overall survival (76% vs 33%; P ¼ .001) and 3-year progression-free survival (73% vs 31%; P ¼ .001). On multivariate analysis, overall survival was influenced by PET status (hazard ratio [HR], 3.35), performance status (HR, 5.15), and type of donor (HR, 6.26 for haploidentical vs sibling; HR, 1.94 for matched unrelated donor vs sibling). CONCLUSIONS: The current results indicated that PET scanning appears to be an accurate tool for assessing prognosis in patients who are eligible for RIC allografting. Cancer 2010;116:5001-11.

show abstract

“…[27][28][29] In addition, use of unrelated donors was introduced some years later after HLA-identical siblings in our transplantation programs for lymphoma, explaining the unexpected ratio of 29:5 sibling:matched-unrelated donors. All these reasons may explain the rather low (18%, that is, 34 out of 150 þ 34 high-risk patients) rate of patients with high-risk features actually receiving tandem auto-allo in our cohort, compared with a theoretical 50% (that is, the probability to find a HLA-identical sibling or unrelated donor).…”

Section: Discussionmentioning

confidence: 99%

Tandem autologous-allo-SCT is feasible in patients with high-risk relapsed non-Hodgkin’s lymphoma

Crocchiolo

Castagna

Fürst

et al. 2012

Bone Marrow Transplant

View full text Add to dashboard Cite

Allo-SCT is used to exploit GVL effect in high-risk relapsed non-Hodgkin's lymphoma (NHL). Here, we retrospectively analyzed 34 high-risk NHL patients who underwent auto-SCT followed closely by reduced-intensity allo-SCT ('tandem auto-allo') from January 2002 to November 2010. The search for an allogeneic donor was started at the beginning of salvage regimen. Median patients' age was 47 (27-68) years; histotypes were: diffuse large B-cell n ¼ 5, follicular n ¼ 14, transformed follicular n ¼ 4, mantle-cell n ¼ 5, plasmocytoid lymphoma n ¼ 1, anaplastic large T-cell n ¼ 2, peripheral T-cell n ¼ 3. Donors were HLA-identical siblings (n ¼ 29) or 10/10-matched unrelated individuals (n ¼ 5). Median interval between auto-SCT and allo-SCT was 77 days . At a median follow-up of 46 (8-108) months since allo-SCT, 5-year OS is 77% (61-93) and PFS is 68% (51-85). Disease relapse or progression occurred in six patients, 100-day TRM was 0%, 2-year TRM incidence was 6%. In conclusion, tandem transplantation is feasible in high-risk NHL patients having a HLA-identical donor. This approach could represent a suitable therapeutic option for those patients with high-risk NHL potentially benefitting from further therapy after auto-SCT. Donor searches should be started promptly whenever such an approach is chosen. Keywords: non-Hodgkin's lymphoma; tandem; autologous; allogeneic; SCT INTRODUCTION High-dose therapy followed by auto-SCT is the standard of care for most relapsed non-Hodgkin's lymphoma (NHL) patients. 1,2 Unfortunately, relapse after auto-SCT remains the most important cause of treatment failure. Allogeneic hematopoietic SCT (allo-SCT) yields lower relapse rates compared with auto-SCT because of its GVL effect 3-6 but on the other hand, its feasibility could be limited by the TRM. 7,8 Some risk factors have been associated with poor outcome after salvage therapy followed by auto-SCT, 1,2,9-11 underlying the need for improving prognosis of these patients. A tandem autologous-allogeneic transplantation approach could have the advantage of combining cytoreduction with GVL effect with the aim of ameliorating the outcome of those patients for whom high-dose chemotherapy followed by auto-SCT gives unsatisfactory results.The aim of this retrospective study is to evaluate the feasibility and safety of tandem 'auto-allo' in poor prognosis NHL patients.

show abstract

Haploidentical stem cell transplantation after a reduced-intensity conditioning regimen for the treatment of advanced hematologic malignancies: posttransplantation CD8-depleted donor lymphocyte infusions contribute to improve T-cell recovery

Cited by 69 publications

References 27 publications

Donor CD4 T cells convert mixed to full donor T-cell chimerism and replenish the CD52-positive T-cell pool after alemtuzumab-based T-cell-depleted allo-transplantation

Donor CD4 T cells convert mixed to full donor T-cell chimerism and replenish the CD52-positive T-cell pool after alemtuzumab-based T-cell-depleted allo-transplantation

Pretransplantation [18‐F]fluorodeoxyglucose positron emission tomography scan predicts outcome in patients with recurrent Hodgkin lymphoma or aggressive non‐Hodgkin lymphoma undergoing reduced‐intensity conditioning followed by allogeneic stem cell transplantation

Tandem autologous-allo-SCT is feasible in patients with high-risk relapsed non-Hodgkin’s lymphoma

Contact Info

Product

Resources

About