scholarly journals α-Interferon with very-low-dose donor lymphocyte infusion for hematologic or cytogenetic relapse of chronic myeloid leukemia induces rapid and durable complete remissions and is associated with acceptable graft-versus-host disease

2004 ◽  
Vol 10 (3) ◽  
pp. 204-212 ◽  
Author(s):  
Eduardus F.M Posthuma ◽  
Erik W.A.F Marijt ◽  
Renee M.Y Barge ◽  
Ronald A van Soest ◽  
Inge O Baas ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Graft Versus Host Disease ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Donor Lymphocyte Infusion ◽  
Host Disease ◽  
Graft Versus Host

scholarly journals Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2761-2763 ◽  
Author(s):  
Jeffrey S. Miller ◽  
Daniel J. Weisdorf ◽  
Linda J. Burns ◽  
Arne Slungaard ◽  
John E. Wagner ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Myeloid Leukemia ◽  
Donor Lymphocyte Infusion ◽  
T Cell Proliferation ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor Lymphocytes ◽  
Acute Graft ◽  
Donor Lymphocyte Infusions

Donor lymphocyte infusions (DLIs) can produce lasting remissions in patients with relapsed chronic myeloid leukemia (CML), but are less effective in non-CML diseases. We hypothesized that lymphodepletion, achieved with cyclophosphamide (Cy) and fludarabine (Flu), would promote in vivo expansion of the infused lymphocytes enhancing their immunologic effects. Fifteen patients with relapsed non-CML disease who received Cy/Flu/DLI were compared with 63 controls who received DLI without chemotherapy. Only the patients receiving Cy/Flu/DLI became lymphopenic at the time of DLI. Compared with controls, patients who received Cy/Flu/DLI developed significantly more grades II to IV (60% vs 24%, P = .01) and grades III to IV acute graft-versus-host disease (GVHD) (47% vs 14%, P = .01) with greater GVHD lethality. In Cy/Flu/DLI patients, T-cell proliferation was elevated at 14 days after DLI. Although these data suggest that chemotherapy-induced lymphodepletion enhances activation of donor lymphocytes, the toxicity needs to be managed before testing whether better disease control can be achieved. This trial was registered at www.clinicaltrials.gov as no. NCT00303693 and www.cancer.gov/clinicaltrials as no. NCT00167180.

Association between BMI-1 expression, acute graft-versus-host disease, and outcome following allogeneic stem cell transplantation from HLA-identical siblings in chronic myeloid leukemia

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 2163-2166 ◽  
Author(s):  
Mohamad Mohty ◽  
Richard M. Szydlo ◽  
Agnes S. M. Yong ◽  
Jane F. Apperley ◽  
John M. Goldman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Chronic Myeloid Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Abstract Expression of CD7, ELA-2, PR-3, and the polycomb group gene BMI-1 reflects the intrinsic heterogeneity and predicts prognosis of patients with chronic myeloid leukemia (CML) who were not treated with allogeneic stem cell transplantation (allo-SCT). This study investigated whether expression of these genes determined outcome following allo-SCT in a cohort of 84 patients with chronic-phase (CP) CML. We found that patients expressing BMI-1 at a “high” level before allo-SCT had an improved overall survival (P = .005) related to a reduced transplantation-related mortality. In multivariate analysis, when adjusted for the European Group for Blood and Marrow Transplantation (EBMT)–Gratwohl score and other prog-nostic factors, there was an independent association between BMI-1 expression and grades 2 to 4 acute graft-versus-host disease (relative risk [RR] = 2.85; 95% confidence interval [CI], 1.3-6.4; P = .011), suggesting that BMI-1 measured prior to allo-SCT can serve as a biomarker for predicting outcome in patients with CP-CML receiving allo-SCT, and may thus contribute to better therapeutic decisions.

Nilotinib as Salvage Therapy In Patients with Chronic Graft Versus Host Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2329-2329
Author(s):  
Louis Terriou ◽  
Leonardo Magro ◽  
Eva De Berranger ◽  
Jean-Pierre Jouet ◽  
Ibrahim Yakoub-Agha
Keyword(s):  
Side Effects ◽  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Graft Versus Host Disease ◽  
Salvage Therapy ◽  
Myeloid Leukemia ◽  
Joint Contracture ◽  
Host Disease ◽  
Graft Versus Host

Abstract Abstract 2329 The mainstay of treatment for Chronic Graft Versus Host Disease (cGVHD) is steroids, but there are limited treatment options for steroid refractory cGVHD particularly in its sclerotic and fibrotic form (ScGVHD). We initially reported the efficacy and safety of imatinib mesylate (IM), a first generation tyrosine kinas' inhibitor, as a salvage therapy for ScGVHD patients (Magro L, et al. Blood, 2009). However, about 50% of the patients (Pts) became refractory or intolerant to IM. Nilotinib, a second generation tyrosine kinas' inhibitor, is labelled for IM resistant and advanced Chronic Myeloid leukemia and could be an attractive alternative to IM especially in refractory and intolerant patients. We studied the clinical outcomes of 7 Pts who developed extensive ScGVHD at our institution. Among them, 5 had received prior IM. Patients' characteristics and transplantation modalities are summarised in table 1. Acute and cGVHD was scored according to standard criteria. All pts but one failed at least 3 lines of prior systemic immunosuppressive therapy. CGVHD features, responses to nilotinib and patients' outcomes are described in table 2. To our knowledge, this is the first report relating the impact of nilotinib on cGVHD setting. Although, tolerance to nilotinib has not been as good as we could expect, this drug appeared to be effective with manageable side-effects in some patients. One of the limitations of this study, is that nilotinib was used in patients with advanced cGVHD. Prospective studies are, therefore, warranted to investigate the efficacy and the tolerance of nilotinib in patients with less advanced disease. Table 1. Patients and transplantation characteristics Case N Age, y Sex, R/D diagnosis Conditioning/Stem cell source GVHD prophylaxis cGVHD sites Immunosuppression before nilotinib 1 30.5 M/F ALL MAC/BM CSA-MTX Mouth, skin eyes,liver CS-CSA-MMF-RTX-EVE 2 31 F/M AA MAC/PBSC CSA-CS-MMF Skin, mouth, eyes,bronchiolitis,joint contacture CS-TAC-MMF-EVE-IM 3 51.6 M/M HODG RIC/PBSC CSA-MTX Skin, mouth CS-CSA-MMF-IM 4 45.3 M/M AML MAC/BM CSA-MTX Skin, mouth, bronchiolitis, joint contracture CS-CSA-MMF-INO-ECP-RTX-AZA-IM 5 57.5 M/M MDS MAC/BM CSA-MTX Skin, bronchiolitis, joint contracture CS-CSA-MMF-RTX-ECP-IM 6 50.3 M/F CML MAC/BM CSA-MTX Skin, mouth, eyes, liver, joint contracture CS-CSA-MMF-ECP-IM 7 53.3 M/M AML MAC/BM CSA-MTX Skin none R/D: recipient/donor; aGVHD: acute graft versus host disease; cGVHD: chronic graft versus host disease; CML: chronic myeloid leukemia; MAC: myeloablative conditioning; BM: bone marrow; PBSC: peripheral blood stem cells; CSA: ciclosporine A; CS: corticosteroids, RIC: reduced intensity conditioning; MMF: mycophenolate mofetyl; AZA: azathioprine; MDS: myelodysplastic syndrome; MTX: metothrexate; RTX: rituximab; ECP: extracorporal photophere-sis; INO: inolimomab; HODG, hodgkin; AA: aplastic anemia; TAC: tacrolimus, ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia.; EVE: everolimus and IM: imatinib mesylate. Table 2. Outcome after nilotinib therapy Case N° Maximal tolerate dose of nilotinib, mg Nilotinb therapy duration at last follow up, mo Side effects/nilotinib discontinuation at last follow up cGVHD status at 2 mo of nilotinib cGVHD response in other organs at last follow up cGVHD status at last follow up Overall follow-up, mo Status at last follow up 1 800 3 None/yes failure – PR 69 alive 2 400 0.5 Pain swallowing, diarrhea/yes failure – progressive 46.8 Died of infection 3 800 2.5 Nausea, diarrhea/yes PR Mouth PR (>90%) 73.1 alive 4 800 7.5 None/yes MR Mouth progressive 72 alive 5 800 1 Cough, dyspnea, muscle cramps/yes PR bronchiolitis PR 59 alive 6 800 0.5 Headache, diarrhea/yes failure – PR 60.3 alive 7 800 7.5 None/no PR – PR 32 alive cGVHD indicates chronic graft versus host disease; PR, partial response and MR, minor response. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease

Blood ◽  
1995 ◽  
Vol 86 (4) ◽  
pp. 1261-1268 ◽  
Author(s):  
S Mackinnon ◽  
EB Papadopoulos ◽  
MH Carabasi ◽  
L Reich ◽  
NH Collins ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Myeloid Leukemia ◽  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Myeloid Leukemia ◽  
Host Disease ◽  
Graft Versus Host ◽  
Cell Dose ◽  
Graft Versus Leukemia

Infusions of large numbers (> 10(8)/kg) of donor leukocytes can induce remissions in patients with chronic myeloid leukemia (CML) who relapse after marrow transplantation. We wanted to determine if substantially lower numbers of donor leukocytes could induce remissions and, if so, whether this would reduce the 90% incidence of graft-versus-host disease (GVHD) associated with this therapy. Twenty-two patients with relapsed CML were studied: 2 in molecular relapse, 6 in cytogenetic relapse, 10 in chronic phase, and 4 in accelerated phase. Each patient received escalating doses of donor leukocytes at 4- to 33-week intervals. Leukocyte doses were calculated as T cells per kilogram of recipient weight. There were 8 dose levels between 1 x 10(5) and 5 x 10(8). Lineage-specific chimerism and residual leukemia detection were assessed using sensitive polymerase chain reaction (PCR) methodologies. Nineteen of the 22 patients achieved remission. Remissions were achieved at the following T-cell doses: 1 x 10(7) (n = 8), 5 x 10(7) (n = 4), 1 x 10(8) (n = 3), and 5 x 10(8) (n = 4). To date, 15 of the 17 evaluable patients have become BCR-ABL negative by PCR. The incidence of GVHD was correlated with the dose of T cells administered. Only 1 of the 8 patients who achieved remission at a T-cell dose of 1 x 10(7)/kg developed GVHD, whereas this complication developed in 8 of the 11 responders who received a T-cell dose of > or = 5 x 10(7)/kg. Three patients died in remission, 1 secondary to marrow aplasia, 1 of respiratory failure and 1 of complications of chronic GVHD. Sixteen patients who were mixed T-cell chimeras before treatment became full donor T-cell chimeras at the time of remission. Donor leukocytes with a T-cell content as low as 1 x 10(7)/kg can result in complete donor chimerism together with a potent graft-versus-leukemia (GVL) effect. The dose of donor leukocytes or T cells used may be important in determining both the GVL response and the incidence of GVHD. In many patients, this potent GVL effect can occur in the absence of clinical GVHD.

Induction of Graft-versus-Host Disease as Immunotherapy for Relapsed Chronic Myeloid Leukemia

1994 ◽  
Vol 330 (2) ◽  
pp. 100-106 ◽  
Author(s):  
David L. Porter ◽  
Mark S. Roth ◽  
Carol McGarigle ◽  
James Ferrara ◽  
Joseph H. Antin
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Graft Versus Host Disease ◽  
Myeloid Leukemia ◽  
Host Disease ◽  
Graft Versus Host

scholarly journals Fatal graft-versus-host disease following HLA-mismatched donor lymphocyte infusion

2001 ◽  
Vol 28 (6) ◽  
pp. 623-625 ◽  
Author(s):  
PJ Amrolia ◽  
K Rao ◽  
O Slater ◽  
A Ramsay ◽  
PA Veys ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Donor Lymphocyte Infusion ◽  
Host Disease ◽  
Graft Versus Host ◽  
Mismatched Donor
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