Waldenström's macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by the presence in patients' serum of an IgM monoclonal component. We report on our experience with 60 WM patients, focusing on their clinical findings, response to treatment, and the possible identification of prognostic factors. Of these patients, 70% presented with fatigue, and lymphadenopathy was observed in 22%, splenomegaly in 18%, hepatomegaly in 13%, and extranodal site of involvement in 6%. Bleeding tendency was seen in 17%, infections in 17%, hyperviscosity syndrome in 12%, and cardiac failure in 25% of the patients. The median of IgM levels was 30 g/l with hypoalbuminemia in 20% of cases, hypogammaglobulinemia in 27%, polyclonal hypergammaglobulinemia in 15%, kappa light-chain restriction in 78%, and Bence-Jones proteinuria in 54%. Anemia was frequent (85%), followed by leukocytosis (18%), lymphocytosis (12%), leukopenia (10%), and thrombocytopenia (10%). Cryoglobulinemia and autoimmune hemolytic anemia were encountered in 5%. In all cases but two, bone marrow was involved. Of 50 patients initially treated with intermittent oral chlorambucil, 46 (92%) responded. Median overall survival was 108 months. Factors associated with adverse prognosis were age > or =65 years (p=0.06), presence of lymphadenopathy (p=0.06), bone marrow infiltration > or =50% (p=0.007), international prognostic index (IPI) > or =3 (p=0.0001), and Morel's scoring system (p=0.04). Concluding, we found in this series of WM patients that chlorambucil is an effective treatment and that the parameters of age, lymphadenopathy, percentage of bone marrow infiltration, IPI, and Morel's scoring system carry prognostic significance.

Sjögren's syndrome (SS) is a chronic autoimmune disease of unknown etiology characterized by lymphocytic infiltration of the exocrine glands and a polyclonal B-cell activation; it is demonstrated by the presence of multiple autoantibodies against organ- and non-organ-specific autoantigens. SS is associated with malignant lymphomas, Waldenstrom's macroglobulinemia and benign monoclonal gammopathy, while its relationship with multiple myeloma is extremely rare. The association between multiple myeloma and rheumatoid arthritis and other autoimmune diseases has been established, but it is not clear why a B-cell proliferation like myeloma occurs more rarely than other B-cell disorders in patients with SS. We describe a patient who presented with multiple myeloma and SS that might have existed for at least 2 years prior to the appearance of myeloma.

Summary:In an attempt to decrease toxicity in high-risk patients undergoing unrelated donor hematopoietic stem cell transplantation (URD HSCT), we tested a combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis with the reduced-intensity conditioning regimen fludarabine/melphalan (Flu/Mel). A total of 22 adult patients with advanced myeloid (n ¼ 15) and lymphoid (n ¼ 7) malignancies were treated. All patients received Flu 25 mg/m 2 for 5 days and Mel 140 mg/m 2 , with CSP 3 mg/kg daily and MMF 15 mg/kg three times a day. The median age was 49 years (range 18-66). Durable engraftment was seen in all but one patient with myelofibrosis. The 1-year nonrelapse mortality was 32%, 27% from GVHD. The cumulative incidence of acute GVHD grade 2-4 and 3-4 was 63 and 41%, respectively. With a median follow-up of 18 months, the disease-free survival (DFS) and overall survival (OS) are 55 and 59%, respectively. For patients with AML and MDS (n ¼ 14), the DFS and OS is 71%. For patients undergoing a second transplant (n ¼ 14), the DFS and OS is 57%. In conclusion, this regimen is associated with acceptable toxicity but high rates of GVHD in high-risk patients undergoing URD HSCT. Encouraging disease control for patients with advanced myeloid malignancies was observed. The applicability of unrelated hematopoietic stem cell transplantation (URD HSCT) for patients with hematological malignancies has been greatly hampered by its early toxicity, with 100-day mortality ranging from 15 to 50%. 1 These statistics have been generated from younger patients (o55 years) with normal organ function, with age and disease status at transplantation largely accounting for the variability in outcome. Older patients and those who have comorbidities or who have failed previous autologous transplants experience even greater toxicity, thus making them extremely high risk or ineligible for this procedure. 2 Reduced-intensity conditioning (RIC) regimens have allowed high-risk patients to undergo allogeneic HSCT with decreased transplant-related toxicity. The RIC regimen fludarabine/melphalan (Flu/Mel), for example, has been used in conjunction with tacrolimus (FK-506) and mini-methotrexate (MTX) as graft-versus-host-disease (GVHD) prophylaxis, for high-risk patients with a variety of hematological malignancies, resulting in a relatively low 100-day nonrelapse mortality (NRM) of 37%. 3 Excellent engraftment was also seen with this regimen (median donor chimerism of 100% at day 30), with an encouraging disease-free survival (DFS) at 1 year of 57 and 49%, for patients with early and advanced disease, respectively. In this series, the probability of grade 2-4 and 3-4 acute GVHD was 0.49 and 0.29, respectively.The combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) has been successfully developed as GVHD prophylaxis, with powerful synergism in animal models, 4 and clinical efficacy in the nonmyeloablative transplant setting. 5,6 In an attempt to further reduce regimen-related toxicity...

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0.21), stage III/ IV (17% vs 12%), any extranodal involvement (27% vs 43%, p = 0.11), any serositis (49% vs 46%), bulky disease (71% vs 75%), LDH levels >twice normal (>2x; 41% vs 39%), anemia (48% vs 42%), leukocytosis ≥10x10 9 /L (31% vs 27%), ESR ≥30 mm/h (78% vs 79%), albumin <4 g/ dL (49% vs 45%), age-adjusted IPI (aaIPI) ≥2 (39% vs 38%) (all p-values >0.40, unless otherwise stated). Among R-CHOP-treated patients 10/43 had treatment failure compared to 5/52 for R-da-EPOCH. One R-da-EPOCH patient developed early-onset acute leukemia with t(9;11) and was counted as event in event-free survival (EFS) analysis. The 2-year freedom from progression (FFP) was 89% vs 77% (p = 0.22), while the 2-year EFS was 86% vs 77% (p = 0.35). With 5 deaths recorded (4 in R-CHOP vs 1 in R-da-EPOCH; all disease related), the 3-year overall survival (OS) was 96% vs 90% (p = 0.27). Among R-CHOP-treated patients, 5 did not receive RT due to chemorefractory disease; 29/38 potentially eligible patients (76%) received RT. Among 46 R-da-EP-OCH-treated patients who had completed final resonse assessment, 5 did not receive RT due to chemorefractory disease; only 6/41 potentially eligible patients (15%) received RT (p < 0.001).