When interleukin-2 (IL-2) binds to the IL-2 receptor (IL2-R) on activated T cells, a soluble portion of the receptor (sIL2-R) is released. After allogeneic bone marrow transplantation (BMT), the serum concentration of sIL2-R may, therefore, be a useful surrogate marker for T cell activation that results in acute graft-versus-host disease (aGVHD). To determine if the sIL2-R concentration is a useful marker to help establish a diagnosis of aGVHD, serial sIL2-R concentrations were measured weekly for 4 weeks in 43 patients after allogeneic BMT. Grafts were from HLA-matched siblings (n = 33), 5/6 HLA-matched siblings (n = 3) or matched unrelated donors (n = 7). GVHD prophylaxis included cyclosporine A (CSA)/methotrexate (MTX) (n = 25), solumedrol/CSA (n = 15), or T cell depletion (n = 3). Twenty-three patients developed aGVHD (Grade I, 7; Grade II, 12; Grade III, 4) a median of 28 days after transplant. There was a significant association between a clinical diagnosis of aGVHD and an increase in the sIL2-R concentration (p < 0.001). The mean percent increase (+/-SE) over baseline for patients with a clinical diagnosis of aGVHD was 294% (+/-57%) by week 2 (n = 12), 431% (+/-116%) by week 3 (n = 14), and 650% (+/-315%) by week 4 (n = 9) after BMT. For each 100% increase over baseline, the likelihood of having aGVHD increased by 18%. Six of 20 patients without aGVHD became critically ill and exhibited marked increases in sIL2-R concentrations, similar to patients with a clinical diagnosis of aGVHD who never became critically ill. Fourteen patients without aGVHD who did not become critically ill exhibited negligible increases of sIL2-R in 2- to 4-week period after BMT. These data suggest that serial measurements sIL2-R concentration are helpful in establishing the diagnosis of aGVHD, but are not useful in the most acutely ill patients.

Summary:Although follicular lymphoma (FL) is generally responsive to conventional-dose chemotherapy, improved survival in patients with this disease has been difficult to demonstrate. High-dose chemo/radiotherapy followed by autologous stem-cell transplantation (ASCT) can improve response rates, although its effects on survival remain controversial. Between 1990 and 2003, we transplanted 49 patients with low-grade FL at our institution. Twenty-two patients (45%) had undergone histologic transformation at the time of ASCT. In all, 44 patients (90%) had relapsed disease and five patients (10%) were resistant to chemotherapy at the time of transplantation. After ASCT, 30 patients (61%) were in complete remission (CR). The median overall survival (OS) has not been reached, while the median event-free survival (EFS) is 2.4 years. At a median follow-up of 5.5 years (longest 12.4 years), a plateau has been reached with 56% of patients remaining alive, and 35% event-free. ASCT was well tolerated except for two (4%) treatment-related deaths. In multivariable analysis, CR after ASCT and age less than 60 years are the best predictors of EFS and OS. ASCT is thus a safe therapeutic approach in FL, resulting in long-term EFS and OS for some patients, even with transformed disease. Bone Marrow Transplantation (2005) 36, 955-961.

Summary:Nonmyeloablative stem cell transplantation (NST) harnesses the graft-versus-tumor effect while minimizing regimen-related toxicity, and can result in donor chimerism and remission. Acute graft-versus-host disease (GVHD) and infections are major complications after sibling NST. Toxicity of unrelated-donor (UD) NST and the most appropriate GVHD prophylaxis in this setting remain poorly defined. We describe 25 patients who received UD-NST conditioned with fludarabine and cyclophosphamide. The first six patients received cyclosporine (Cs) and mycophenolate mofetil (MMF) (n ¼ 5) or methotrexate (MTX) (n ¼ 1) as GVHD prophylaxis (group 1) and all developed grade III-IV acute GVHD. The next 19 patients received the same conditioning regimen with the addition of alemtuzumab, and all received Cs/MTX post-transplant. Engraftment and donor chimerism were achieved in all but one evaluable patient. In all, 15 patients died: five of six deaths in group 1 were attributable to acute GVHD, while deaths in group 2 were due to infection or progressive disease (P ¼ 0.05). The combination of Cs/MMF is inadequate GVHD prophylaxis for UD-NST. The use of Cs, MTX, and alemtuzumab eliminated severe acute GVHD; its impact on response merits further study. Bone Marrow Transplantation (2005) 35, 921-926.

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