Post-hematopoietic stem cell transplantion immune-mediated cytopenias.

Immune-mediated cytopenias after allogeneic stem cell transplantation can be categorized as either alloimmune when host or donor immunity reacts against donor or host elements, respectively, or autoimmune when donor immunity reacts against donor hematopoietic tissue, owing to poorly understood mechanisms that result in severe impairment of central and peripheral tolerance. Immune cytopenias are manifested as monolineage or more rarely as bilineage cytopenias, and are usually mediated through humoral immune mechanisms. On the contrary, immune-mediated pancytopenia is a rare event with only few cases reported in the literature. The exact pathogenesis of immune pancytopenia is not well known although it is possible that cellular immunity may play a significant role. The importance of these syndromes lies in the fact that they can cause severe morbidity and mortality. Differential diagnosis from other causes of post-transplant pancytopenia is of extreme value because these disorders can respond to various treatment modalities.

A non-myeloablative conditioning regimen in allogeneic stem cell transplantation from related and unrelated donors in elderly patients.

We describe our experience with the use of a single non-myeloablative preparative regimen in stem-cell transplantation (NST) in 37 heavily pretreated patients > or =55 years. The conditioning regimen consisted of fludarabine, low-dose busulfan, and antithymocyte globulin. Acute graft-versus-host disease (GVHD) grade III-IV and chronic GVHD developed in 15.6% and 44.4% of cases, respectively. With a median follow-up period of 22 (range 3-113) months, the 1-year overall survival and disease-free-survival were 55% and 53%, respectively, while the overall non-relapse mortality was 35%. In conclusion, reduced intensity stem cell transplantation is feasible and effective in patients > or =55 years. Age per se, should no longer be considered as a contra-indication to stem cell transplantation.

Allogeneic stem cell transplantation for severe acquired aplastic anaemia using a fludarabine-based preparative regimen.

We reviewed our experience in the treatment of 13 patients with severe acquired aplastic anaemia, using a newly developed non-myeloablative regimen consisting of fludarabine (total dose 180 mg/m2), cyclophosphamide (total dose 120 mg/kg), and antithymocyte globulin (total dose 40 mg/kg). All except one patient received multiple transfusions and had failed prior immunosuppressive treatment. Twelve out of 13 patients achieved sustained engraftment. One patient was not evaluable for engraftment because of early death on day +10. None of the patients developed graft failure. Mucositis of mild-to-moderate severity was the only observed regimen-related toxicity. The cumulative incidence of acute graft-versus-host disease (GvHD) grade II-IV and III-IV was 8.3% and 0%, respectively. With a median follow-up period of 45 months, the 5-year overall survival probability was 84%. Eight out of 11 surviving patients have been followed for more than 1 year and only one developed limited chronic GvHD. All patients enjoy a normal life style, with a Karnofsky score of 100%, and all except three, followed for 3, 5 and 6 months respectively, are free of any immunosuppressive medication. The results of this study look promising, while prospective clinical trials may be required to confirm the benefits of this regimen as an alternative to existing protocols.

Successful transplantation of haploidentically mismatched peripheral blood stem cells using CD133+-purified stem cells.

OBJECTIVE: For recipients of haploidentically mismatched stem cell allografts, T-cell depletion is mandatory to prevent lethal graft-vs-host disease (GVHD). Prevention of GVHD can be accomplished by negative selection of T cells or positive selection of stem cells. Recently, a new method for positive selection of stem cells was introduced using monoclonal antibodies against CD133 antigen. We report five cases of successful application of immunomagnetic separation of CD133+ stem cells for haploidentically mismatched allogeneic stem cell transplantation. METHODS: Five patients with high-risk hematological malignancies, ages 7 to 63 years old (median, 17 years), underwent peripheral blood stem cell transplantation from haploidentically mismatched related donors. Conditioning protocol was tailored according to patient clinical situation and included combination of treosulfan/fludarabine/thiotepa/melphalan/Mabcampath. Two patients did not get thiotepa. One of them received a protocol that included infusion of 4.4 x 10(7) blood mononuclear cells from the donor (day -9), followed by a combination of fludarabine/cyclophosphamide/busulfex/MabCampath. Separation of CD133+ stem cells was done using CliniMACS with Miltenyi's CD133 reagent. RESULTS: The procedure was well tolerated by all patients. Early 3-lineage engraftment was documented and none exhibited immune-mediated rejection. Time to recovery of absolute neutrophils count above 0.5 x 10(9)/L and 1.0 x 10(9)/L was 10 to 15 days (median, 14) and 11 to 29 days (median, 15), respectively. Time for platelet recovery to values greater than 20 x 10(9)/L and greater than 50 x 10(9)/L ranged from 12 to 25 days (median, 13.5), and from 14 to 34 days (median, 16), respectively. Transplant-related mortality did not occur in any of the patients. CONCLUSION: Our successful pilot trial suggests that positive selection of CD133+ stem cells may be a useful method for safe transplantation with haploidentically mismatched stem cell allografts while avoiding lethal acute and chronic GVHD. Future studies will be required to assess the clinical benefits of stem cell purification with CD133+ in comparison with CD34+ stem cells.

Spinal epidural lipomatosis following haploidentical allogeneic bone marrow transplantation for non-Hodgkin lymphoma.

OBJECTIVES: Spinal epidural lipomatosis, is a very rare condition, usually seen as an uncommon complication of Cushing's syndrome secondary to chronic steroid therapy leading to increased fat deposits in the epidural space. CASE REPORT: We report the first documented case of acute symptomatic spinal epidural lipomatosis in a patient with relapsed non-Hodgkin lymphoma. The patient underwent an allogeneic bone marrow transplantation (BMT) and a month of steroid treatment for acute graft vs. host disease (GvHD). He presented with a mild to moderate Cushing's syndrome and minimal obesity. He progressed rapidly to paraparesis, sensory deficit, urinary incontinence and finally respiratory arrest complicated with staphylococcal sepsis. CONCLUSION: Epidural lipomatosis, with subacute thecal sac compression, is a possible life-threatening complication of relatively short-term systemic glucocorticoid therapy for GvHD in BMT setting.

Intra-arterial catheter directed therapy for severe graft-versus-host disease.

Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation (BMT), resulting in death in the majority of steroid-resistant patients. We assessed the efficacy of regional intra-arterial treatment in patients with resistant hepatic and/or gastrointestinal (GI) GVHD. In total, 15 patients with steroid resistant grade 3-4 hepatic (n = 4), gastrointestinal (GI) (n = 8) GVHD or both (n = 3) were given intra-arterial treatment. Patients with hepatic GVHD received methotrexate and methylprednisolone into the hepatic artery. Patients with GI GVHD were treated with infusions of methylprednisolone into the superior and inferior mesenteric arteries. Two patients with pronounced upper GI symptoms also received upper GI treatment. In total, 25 procedures were carried out (range 1-3 per patient). Hepatic response was observed in four out of seven (57%) patients with hepatic GVHD, three (43%) featuring good response. Complete responses were observed in nine (82%) GI GVHD patients, with median time to initial and complete response of 3 d (range 1-7) and 15.8 d (range 4-33) respectively. Regional treatment of severe GVHD with intra-arterial treatment appears to be effective and safe. GI treatment maybe more effective than intrahepatic treatment. Early administration of isolated intra-arterial therapy in high-risk patients may further improve the outcome and reduce untoward effects of systemic immunosuppressive treatment.