ABSTRACT
Monitoring of Epstein-Barr virus (EBV) load and pre-emptive rituximab is an appropriate approach to prevent post-transplant lymphoproliferative disease (PTLD) occurring after hematopoietic stem cell transplantation (HSCT). This pre-emptive approach, based on EBV-DNA monitoring through a quantitative polymerase chain reaction, was applied to 101 consecutive patients who underwent allo HSCT at our Institute (median age 50). A single infusion of rituximab was administered to 11 of 16 patients who were at high risk for progression to PTLD, defined as a DNA value >10 000 copies/mL. All patients cleared EBV DNAemia, without any recurrences. Main factors significantly associated with high risk for PTLD were as follows: (i) unrelated vs. sibling (26% vs. 7%; p = 0.011); (ii) T-cell depletion (29% vs. 6%; p = 0.001); (iii) graft versus host disease (GVHD; 30% vs. 7%; p = 0.002); and (iv) cytomegalovirus (CMV) reactivation (29% vs. 4%; p = 0.001). Multivariate analysis showed that CMV reactivation was the only independent variable associated with EBV reactivation. We conclude that: (i) a single infusion of rituximab is able to prevent the risk of progression into EBV-related PTLD; and (ii) CMV reactivation is strongly associated with EBV reactivation; therefore, an intensive EBV monitoring strategy could be advisable only in case of CMV reactivation.
Subject(s)
Cytomegalovirus Infections/complications , Epstein-Barr Virus Infections/etiology , Graft vs Host Disease/etiology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Herpesvirus 4, Human/physiology , Lymphoproliferative Disorders/etiology , Virus Activation , Adult , Aged , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Cohort Studies , Cytomegalovirus/pathogenicity , Cytomegalovirus Infections/virology , DNA, Viral/genetics , Epstein-Barr Virus Infections/drug therapy , Female , Follow-Up Studies , Graft vs Host Disease/drug therapy , Humans , Immunologic Factors/therapeutic use , Lymphoproliferative Disorders/drug therapy , Male , Middle Aged , Prognosis , Risk Factors , Rituximab , Transplantation, Homologous , Young AdultABSTRACT
The benefits of allografting noted in some malignant diseases might be safely extended to metastatic breast cancer by a combination of cytoreduction with high-dose chemotherapy (HDT) and autologous stem-cell transplant (ASCT) with graft-versus-tumour effect mediated by transplanted donor immune cells with nonmyeloablative allografting (reduced intensity conditioning transplantation, RICT). 17 patients with heavily pretreated disease were given tandem transplants. 13 patients sustained donor engraftment. Three had partial remission after HDT and ASCT and complete remission after RICT; they achieved full chimerism and all developed graft-versus-host disease (GVHD) before regression of cancer. Another patient did not respond to HDT and ASCT but had partial remission after RICT, giving an overall response rate of 24%. Five patients had grade II or higher acute GVHD and five had extensive chronic GVHD. No non-relapse-related deaths occurred during the first 100 days. Five patients (29%) were alive 90-2160 days (median 1320) after RICT. This two-step approach is feasible in patients with metastatic breast cancer.
Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/secondary , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/pathology , Hematopoietic Stem Cell Transplantation , Transplantation Conditioning , Adult , Chimerism , Combined Modality Therapy , Female , Graft vs Host Disease , Graft vs Tumor Effect , Humans , Lymphocyte Transfusion , Middle Aged , Mitoxantrone/administration & dosage , Thiotepa/administration & dosage , Transplantation Conditioning/methods , Transplantation, Autologous , Transplantation, HomologousABSTRACT
Sixteen patients with stage III multiple myeloma (MM) and a median age of 51 years were treated with autografting followed by reduced intensity conditioning allotransplantation (RICT). Nine patients are alive in remission at a median of 30 months after their transplants, one patient is alive in relapse and 6 patients died of progressive disease (5) or extensive chronic graft-versus-host disease, infections and progressive disease (1). We suggest that this two-step approach is feasible and it has strong anti-myeloma activity.
Subject(s)
Multiple Myeloma/therapy , Peripheral Blood Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Transplantation, Autologous/methods , Transplantation, Homologous/methods , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Cyclophosphamide/pharmacology , Disease Progression , Disease-Free Survival , Feasibility Studies , Female , Graft vs Host Disease/etiology , Graft vs Host Disease/mortality , Graft vs Host Disease/prevention & control , Granulocyte Colony-Stimulating Factor/pharmacology , Humans , Immunosuppressive Agents/therapeutic use , Infections/etiology , Infections/mortality , Male , Melphalan/therapeutic use , Middle Aged , Multiple Myeloma/drug therapy , Postoperative Complications/mortality , Remission Induction , Salvage Therapy , Survival Analysis , Treatment Outcome , Vidarabine/analogs & derivatives , Vidarabine/therapeutic use , Whole-Body IrradiationABSTRACT
Autografting (or autologous stem cell transplant [ASCT]) followed by "rescue" with Philadelphia chromosome (Ph)-negative hematopoietic progenitor cells (HPC) remains a good procedure to guarantee prolonged survival for patients mobilized and autografted soon after diagnosis. Among 50 autografted patients who were treated with interferon alpha (IFN-alpha) and imatinib (for cytogenetic relapse after IFN-alpha), 41 are alive at a median of 51 months (range, 8 to 106 months). Twenty-eight (56%) patients maintain major cytogenetic remission after ASCT + IFN-alpha +/- imatinib. Such results are probably better than those achieved by IFN-alpha alone and are similar to the best results obtained in younger patients after allografting with human leukocyte antigen (HLA)-identical sibling donors. The integration of imatinib, during the coming years, into an autografting procedure could represent important progress towards developing a cure for chronic myeloid leukemia (CML) patients who cannot undergo conventional allografting.