Second autologous transplant with cyclosporin/interferon α-induced graft versus host disease for patients who have failed first-line consolidation

Streetly, Mathew; Kazmi, Majid; Radia, Deepti; Hoyle, Charles H.V.; Schey, Stephen

doi:10.1038/sj.bmt.1704484

Cited by 7 publications

(4 citation statements)

References 34 publications

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“…Nevertheless, their findings are encouraging with reported 5 year PFS and OS of 49% and 54%, respectively. The ability to demonstrate chemosensitivity appears to be an important prognostic feature in several other smaller case series (14, 17, 18). It should be noted that TRM appears to be much higher for HL patients than might be expected for other lymphoma populations.…”

Section: Discussionmentioning

confidence: 92%

Second Autologous Stem Cell Transplantation for Relapsed Lymphoma after a Prior Autologous Transplant

Smith

Besien

Carreras

et al. 2008

Biology of Blood and Marrow Transplantation

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We determined treatment-related mortality (TRM), progression free survival (PFS), and overall survival (OS) after a second autologous HCT (HCT2) for patients with lymphoma relapse after a prior HCT (HCT1). Outcomes for patients with either Hodgkin lymphoma (HL, n=21) or non-Hodgkin lymphoma (NHL, n=19) receiving HCT2 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) were analyzed. The median age at HCT2 was 38 years (range, 16–61) and 22 (58%) patients had a Karnofsky performance score less than 90. HCT2 was performed >1 year after HCT1 in 82%. The probability of TRM at day 100 was 15% (95% CI, 3–22%). The 1, 3 and 5 yr probabilities of PFS were 50% (95% CI, 34–66%), 36% (95% CI, 21–52%) and 30% (95% CI, 16–46%), respectively. Corresponding probabilities of survival were 65% (95% CI, 50–79%), 36% (95% CI, 22–52%) and 30% (95% CI, 17–46%), respectively. At a median follow up of 72 months (range, 12–124 months) after HCT2, 29 patients (73%) have died, 18 (62%) secondary to relapsed lymphoma. The outcomes of patients with HL and NHL were similar. In summary, this series represents the largest reported group of patients with relapsed lymphomas undergoing SCT2 following failed SCT1, and with long-term follow-up. Our series suggests that SCT2 is feasible in patients relapsing after prior HCT1, with a lower TRM than that reported for allogeneic transplant in this setting. HCT2 should be considered for patients with relapsed HL or NHL after HCT1 without alternative allogeneic stem cell transplant options.

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Section: Discussionmentioning

confidence: 92%

Second Autologous Stem Cell Transplantation for Relapsed Lymphoma after a Prior Autologous Transplant

Smith

Besien

Carreras

et al. 2008

Biology of Blood and Marrow Transplantation

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“…[17][18][19] The ability of the cytokine to modulate GVHD and GVL after allogeneic BM transplantation has been described primarily in anecdotal case series and although difficult to interpret, clear cases of disease control are evident. [20][21][22] In this study, we have demonstrated that type I-IFN signaling plays an important role in both GVHD and GVL responses. Importantly, the effects of the cytokine are pleiotropic, with differential effects on immune outcomes mediated by donor CD4 ϩ and CD8 ϩ T cells.…”

Section: Discussionmentioning

confidence: 99%

Type I-IFNs control GVHD and GVL responses after transplantation

Robb

Kreijveld

Kuns

et al. 2011

Blood

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Although the effects of type II-IFN (IFN-␥) on GVHD and leukemia relapse are well studied, the effects of type I-interferon (type I-IFN, IFN-␣/␤) remain unclear. We investigated this using type I-IFN receptordeficient mice and exogenous IFN-␣ administration in established models of GVHD and GVL. Type I-IFN signaling in host tissue prevented severe colontargeted GVHD in CD4-dependent models of GVHD directed toward either major histocompatibility antigens or multiple minor histocompatibility antigens. This protection was the result of suppression of donor CD4 ؉ T-cell proliferation and differentiation. Studies in chimeric recipients demonstrated this was due to type I-IFN signaling in hematopoietic tissue. Consistent with this finding, administration of IFN-␣ during conditioning inhibited donor CD4 ؉ proliferation and differentiation. In contrast, CD8-dependent GVHD and GVL effects were enhanced when type I-IFN signaling was intact in the host or donor, respectively. This finding reflected the ability of type I-IFN to both sensitize host target tissue/leukemia to cell-mediated cytotoxicity and augment donor CTL function. These data confirm that type I-IFN plays an important role in defining the balance of GVHD and GVL responses and suggests that administration of the cytokine after BM transplantation could be studied prospectively in patients at high risk of relapse. (Blood. 2011;118(12):3399-3409) IntroductionAlthough allogeneic BM transplantation is curative therapy for a majority of hematologic malignancies, its application has been limited by the development of GVHD. GVHD is the result of immunologic damage to the host tissue by alloreactive T cells from the incoming donor graft. Unfortunately, the development of detrimental GVHD is closely intertwined with therapeutic GVL responses. GVL responses are important for eradication of residual host malignancy and are primarily mediated by alloreactive donor T and natural killer (NK) cells. Therapeutic approaches to separate these phenomena are urgently needed.The IFNs were first discovered as a result of their capacity to confer cell resistance to viral infection. 1 There are 2 distinct IFN types, type I and type II, and although both groups induce antiviral defense mechanisms in cells, primarily by limiting replication, they exhibit distinct immunologic properties. After allograft rejection, it is well established that the type II-IFN, IFN-␥, is a dominant Th1 cytokine, exerting pleotropic effects on both hematopoietic and nonhematopoietic cells. Importantly, IFN-␥ has differential effects on both donor and host tissue, with a protective role dominating within GVHD of the lung and pathogenic effects dominating in the gastrointestinal tract. [2][3][4] In addition, the cellular subsets producing IFN␥ and the timing of production may also impact the effect of the cytokine after BM transplantation. 5 In contrast, the role of type I-IFN after BM transplantation remains largely unknown.All type I-IFNs act through the same receptor, which is composed of 2 subunits, IFNAR...

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“…Streetly et al 36 approached the problem of relapse after second auto-HSCT using the immunomodulatory agents, CYA and IFN-g, to induce a graft-vs-tumor (GVT) effect in 10 patients (7 NHL and 3 HL). Histological changes consistent with cutaneous GVHD were observed in three patients.…”

Section: Therapeutic Options For Patients With Lymphoma Who Relapse Amentioning

confidence: 99%

Second hematopoietic SCT for lymphoma patients who relapse after autotransplantation: another autograft or switch to allograft?

Freytes

Lazarus

2009

Bone Marrow Transplant

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Second autologous transplant with cyclosporin/interferon α-induced graft versus host disease for patients who have failed first-line consolidation

Cited by 7 publications

References 34 publications

Second Autologous Stem Cell Transplantation for Relapsed Lymphoma after a Prior Autologous Transplant

Second Autologous Stem Cell Transplantation for Relapsed Lymphoma after a Prior Autologous Transplant

Type I-IFNs control GVHD and GVL responses after transplantation

Second hematopoietic SCT for lymphoma patients who relapse after autotransplantation: another autograft or switch to allograft?

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