Low-dose alemtuzumab for GvHD prevention followed by prophylactic donor lymphocyte infusions in high-risk leukemia.

We analyzed the use of low-dose alemtuzumab in a cohort of 158 consecutive patients who underwent allogeneic PBSC transplantation. Patients with high-risk acute leukemia were prospectively screened for prophylactic donor lymphocyte infusion (pDLI). Lymphocytes were administered repeatedly at low and non-escalating doses (0.5-1 × 106/kg). Low-dose alemtuzumab was effective in prevention of acute GvHD after sibling or well-matched unrelated transplantation, whereas a more intensified approach was needed after mismatched transplantation. The cumulative incidence of chronic moderate/severe chronic-GvHD (cGvHD) was 15.6%. In total, 63 high-risk leukemia patients were eligible for pDLI. Only 1 out of the 39 pDLI recipients relapsed as compared with 7 out of the 24 recipients, who did not receive pDLI due to logistical hurdles. In multivariate analysis, the use of adjuvant lymphocyte therapy was significantly associated with reduced incidence of relapse and improved disease-free survival. In summary, low-dose alemtuzumab confers to a low cGvHD incidence and the administration of pDLIs in this context is very likely to reduce relapse risk in high risk leukemia patients. This is translated in an estimated 5-year probability of GvHD-free and relapse-free survival of 43.3% for the 136 leukemia patients.

Pharmacokinetics and clinical activity of very low-dose alemtuzumab in transplantation for acute leukemia.

The optimal dose of in vivo-administrated alemtuzumab in the allogeneic transplantation setting has not been defined. We report our experience on 37 patients with high-risk diseases, mainly acute leukemia (AML 23, ALL 10 patients), who underwent sibling (49%) or unrelated (51%) PBSCT (35 patients), and received a total dose of only 10-20 mg Campath-1H as part of the conditioning, and post-transplant CYA without MTX. The neutrophil and especially the platelet engraftment were rapid. There were only two grade III-IV acute GvHD cases, which occurred in unrelated transplants in the Campath-10 cohort. Chronic GvHD developed in six cases (17%) and was limited to skin in five of them. After a median follow-up of 371 days (59-1191), 70% patients are alive and in CR (Karnofsky 100%), and 11 died (TRM n=6, relapse n=5). From the five patients relapsed, three were at advanced stage at transplant and four underwent sibling HCT with the higher (20 mg) alemtuzumab dose. With the 10 mg alemtuzumab schedule (5 mg/day at days -2 and -1) we achieve at day of transplantation low but still lymphotoxic alemtuzumab serum concentrations (176 ng/mL), whereas levels declined fast thereafter, and at engraftment nearly no Campath antibody remained in the patient's serum.

Human herpesvirus 6-related pure red cell aplasia, secondary graft failure, and clinical severe immune suppression after allogeneic hematopoietic cell transplantation successfully treated with foscarnet.

Human herpesvirus 6 (HHV-6) is frequently detected after allogeneic hematopoietic cell transplantation (allo-HCT); however, the clinical interpretation of HHV-6 viremia in a transplant patient is challenging as it may signify asymptomatic reactivation, chromosomal integration of the virus genome in the donor or recipient with no clinical significance, or severe HHV-6 disease. Here we present a case of HHV-6 disease after allo-HCT presenting as pure red cell aplasia, secondary graft failure, and severe immunosuppression causing multiple severe bacterial super-infections. Examination of pre-transplant patient and donor samples as well as serial determination of HHV-6 DNA copy numbers after transplantation were necessary to definitively interpret HHV-6 viremia as active HHV-6 infection with a causative role in pancytopenia and immune suppression. Foscarnet treatment resulted both in viral load decline and disappearance of HHV-6-related bone marrow suppression and predisposition to severe infections. Clinicians should be aware of the wide array of clinical manifestations and the diagnostic pitfalls of post-transplant HHV-6 disease. These issues are extremely challenging, as they may result either in dangerous underestimation of HHV-6 disease or in the institution of unnecessary antiviral therapy. Late bone marrow aplasia and late severe infections after allo-HCT without other obvious causes may be HHV-6 related.