ABSTRACT
BACKGROUND: Gemcitabine is currently the standard chemotherapy for the adjuvant treatment of pancreatic cancer. This chemotherapeutic agent is generally well-tolerated, myelosuppression and gastrointestinal toxicity being common side effects. Nevertheless, gemcitabine-induced pulmonary toxicity has been rarely reported. Despite its low incidence, the spectrum of pulmonary injury is wide, including potentially fatal conditions. We report a case of acute interstitial pneumonia related to gemcitabine, completely solved with Imatinib Mesylate (IM). CASE PRESENTATION: The patient was a 69-year-old man, who developed a hypoxemic respiratory distress during adjuvant treatment with gemcitabine for stage IIA pancreatic cancer. The nonspecific diffuse alveolar involvement found on computed tomography (CT), together with the negative tests for infectious aetiology and the continuing severe respiratory failure despite a long course of broad-spectrum therapy, suggested gemcitabine-induced acute pneumonia as the most likely diagnosis. Thus, after the failure of steroids and all other conventional therapies, the patient was treated with imatinib mesylate on the basis of its activity in the management of graft-versus-host-induced lung fibrosis. A follow-up CT scan of chest one month later showed complete resolution of pneumonia. CONCLUSION: Despite the low frequency of serious pulmonary toxicity, gemcitabine widespread use warns clinicians to consider this life-threatening toxicity. The favourable clinical outcome with IM treatment was remarkable, warranting additional study of IM in the treatment of lung fibrosis.
Subject(s)
Antimetabolites, Antineoplastic/adverse effects , Deoxycytidine/analogs & derivatives , Imatinib Mesylate/therapeutic use , Lung Diseases, Interstitial/chemically induced , Lung Diseases, Interstitial/drug therapy , Pneumonia/chemically induced , Pneumonia/drug therapy , Protein Kinase Inhibitors/therapeutic use , Deoxycytidine/adverse effects , Humans , Lung Diseases, Interstitial/diagnosis , Male , Pneumonia/diagnosis , Tomography, X-Ray Computed , Treatment Outcome , GemcitabineABSTRACT
A non myeloablative conditioning with total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) was shown to protect against graft-versus-host disease (GVHD). To evaluate the effects of TLI-ATG in a multicenter study, 45 heavily pretreated patients, median age 51, with lymphoid (n = 38) and myeloid (n = 7) malignancies were enrolled at 9 centers. Twenty-eight patients (62%) received at least 3 lines of treatment before allografting, and 13 (29%) had refractory/relapsed disease at the time of transplantation. Peripheral blood hematopoietic cells were from HLA identical sibling (n = 30), HLA-matched (n = 9), or 1 antigen HLA-mismatched (n = 6) unrelated donors. A cumulative TLI dose of 8 Gy was administered from day -11 through -1 with ATG at the dose of 1.5 mg/kg/day (from day -11 through -7). GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. Donor engraftment was reached in 95% of patients. Grade II to IV acute GVHD (aGVHD) developed in 6 patients (13.3%), and in 2 of these patients, it developed beyond day 100. Incidence of chronic GVHD (cGVHD) was 35.8%. One-year nonrelapse mortality was 9.1%. After a median follow-up of 28 months (range, 3-57 months) from transplantation, median overall survival was not reached, whereas median event-free survival was 20 months. This multicenter experience confirms that TLI-ATG protects against GVHD and maintains graft-vs-tumor effects.
Subject(s)
Antilymphocyte Serum/therapeutic use , Graft vs Host Disease/prevention & control , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Transplantation Conditioning/methods , Adult , Aged , Antilymphocyte Serum/pharmacology , Cyclosporine/pharmacology , Cyclosporine/therapeutic use , Female , HLA Antigens/immunology , Hematologic Neoplasms/immunology , Hematologic Neoplasms/mortality , Histocompatibility , Humans , Male , Middle Aged , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/pharmacology , Mycophenolic Acid/therapeutic use , Recurrence , Severity of Illness Index , Survival Analysis , Transplantation, Homologous , Whole-Body IrradiationABSTRACT
Reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation (HCT) allowed the existence of an allogeneic cell-mediated antitumor effect in metastatic colorectal cancer (mCRC) to be explored. We report on 39 patients with progressing mCRC treated with different RIC regimens in a multicenter clinical trial of the European Bone Marrow Transplantation Group. Disease status at transplant was progressive disease (PD) in 31 patients (80%), stable disease (SD) in 6 (15%), and partial response (PR) in 2 (5%). All patients engrafted (median donor T cell chimerism of 90% at day +60). Transplant-related morbidities were limited. Grades II-IV acute graft-versus-host disease (aGVHD) occurred in 14 patients (35%) and chronic GVHD (cGVHD) in 9 patients (23%). Transplant-related mortality occurred in 4 patients (10%). The best tumor responses were: 1 complete response (CR) (2%), 7 PR (18 %), and 10 SD (26%), giving an overall disease control in 18 of 39 patients (46%). Allogeneic HCT after RIC is feasible; the collected results compared favorably in terms of tumor response with those observed using conventional approaches beyond second-line therapies. The study of an allogeneic cell based therapy in less advanced patients is warranted.
