Interaction between KIR3DS1 and HLA-Bw4 predicts for progression-free survival after autologous stem cell transplantation in patients with multiple myeloma.

Natural killer (NK) cells exert antimyeloma cytotoxicity. The balance between inhibition and activation of NK-cells played by the inherited repertoire of killer immunoglobulin-like receptor (KIR) genes therefore may influence prognosis. One hundred eighty-two patients with multiple myeloma (MM) were analyzed for KIR repertoire. Multivariate analysis showed that progression-free survival (PFS) after autologous stem cell transplantation (ASCT) was significantly shorter for patients who are KIR3DS1(+) (P = .01). This was most evident for patients in complete or partial remission (good risk; GR) at ASCT. The relative risk (RR) of progression or death for patients with KIR3DS1(+) compared with KIR3DS1(-) was 1.9 (95% CI, 1.3-3.1; P = .002). The most significant difference in PFS was observed in patients with GR KIR3DS1(+) in whom HLA-Bw4, the ligand for the corresponding inhibitory receptor KIR3DL1, was missing. Patients with KIR3DS1(+) KIR3DL1(+) HLA-Bw4(-) had a significantly shorter PFS than patients who were KIR3DS1(-), translating to a difference in median PFS of 12 months (12.2 vs 24 months; P = .002). Our data show that KIR-human leukocyte antigen immunogenetics represent a novel prognostic tool for patients with myeloma, shown here in the context of ASCT, and that KIR3DS1 positivity may identify patients at greater risk of progression.

LACE-conditioned autologous stem cell transplantation for relapsed or refractory diffuse large B-cell lymphoma: treatment outcome and risk factor analysis from a single centre.

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a recognized treatment option for patients with relapsed diffuse large B-cell lymphoma. We have analysed 51 patients who underwent ASCT after LACE (lomustine (CCNU), cytarabine (Ara-C), cyclophosphamide, etoposide) conditioning for relapsed (n = 34, 67%) or primary refractory (n = 17, 33%) diffuse large B-cell lymphoma. With a median follow-up of 60 months (range 2-216) the probabilities of overall survival (OS) and progression-free survival (PFS) at 5 years were 47 and 42%, respectively. The cumulative treatment-related mortality was 10% (n = 5). Probabilities for OS and PFS at 5 years were 56 and 50% for patients with chemosensitive and 29 and 27% for patients with chemorefractory disease. In multivariate analysis abnormal pre-ASCT levels of C-reactive protein (>5 mg/L) were identified as a risk factor for worse OS, whereas abnormal pre-ASCT levels of C-reactive protein and chemoresistance predicted inferior PFS. LACE followed by ASCT is an effective treatment for approximately half of patients with chemosensitive relapsed diffuse large B-cell lymphoma, and a proportion of chemorefractory patients also benefit.

Incidence of hyperthyroidism after unrelated donor allogeneic stem cell transplantation.

We report on three patients who developed overt thyrotoxicosis after volunteer unrelated donor bone marrow transplantation for Philadelphia chromosome positive chronic myeloid leukemia shortly after the onset of chronic graft versus host disease. In all three cases, the etiology of hyperthyroidism is likely to be a combination of toxic factors and an immune process. Systematic evaluation of thyroid function tests in 97 unrelated allograft recipients from our center who survived at least 100 days from stem cell or bone marrow transplantation for hematological diseases gave a rate of overt thyrotoxicosis at 3.1% in this cohort.

Salvage autologous stem cell transplantation for multiple myeloma relapsing or progressing after up-front autologous transplantation.

Progression or relapse occurs in the vast majority of patients with multiple myeloma (MM) who undergo up-front autologous hematopoietic cell transplantation (AHCT1), which remains a cornerstone of treatment in the era of novel agents. Limited data are available regarding the value of salvage therapy with a second AHCT (AHCT2) in patients who relapse/progress after AHCT1. We analyzed the outcome of 83 patients who underwent salvage AHCT2 between 1994 and 2011. Most patients (77%) had received treatment with novel agents between AHCT1 and AHCT2, and 28% of patients were from ethnic minority groups. Median overall survival (OS) from AHCT2 was 31.5 months (95% confidence interval [CI]: 22-41), and median progression-free survival (PFS) was 15.5 months (95% CI: 11-20). In multivariate analysis, only disease status (≥ PR) at AHCT2 was associated with better OS. The 3-year OS rates for patients receiving AHCT2 in > PR and PR were 85.9% (95% CI: 61-96) and 51.3% (95% CI: 34-68), respectively. Disease status at AHCT2 and time to progression/relapse after AHCT1 were associated with PFS in multivariate analysis. In summary, salvage AHCT2 is an effective treatment option in patients with chemosensitive relapse/progression and prolonged remission after a prior autograft.

A long-term durable remission with high-dose therapy and autologous stem cell transplant for stage IVB HIV-associated Hodgkins disease.

A 44-year-old man with relapsed HIV-associated stage IV nodular sclerosing Hodgkin's disease underwent high-dose therapy with autologous stem cell transplantation. The transplant was uncomplicated and the patient remains in complete remission at 59 months. Autologous stem cell transplantation is safe in HIV patients and can achieve long-term durable remissions in Hodgkin's disease.