Hypercalcemia is associated with a poor prognosis in lymphoma a retrospective monocentric matched-control study and extensive review of published reported cases

Annals of Hematology - The prognostic significance of hypercalcemia in lymphoma has only been studied on small series to date. We conducted a retrospective, monocentric, matched-control study that...     

High-dose therapy and autologous stem-cell transplantation can improve event-free survival for indolent lymphoma: a study using patients as their own controls

BACKGROUND: High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) remain controversial for indolent lymphoma patients. METHODS: The study was designed to evaluate the benefit of this strategy by retrospectively comparing for each patient the event-free survival (EFS) after ASCT with the duration of the disease phase just before the phase including ASCT (ie, the last qualifying phase, LQP). RESULTS: A total of 109 indolent lymphoma (mostly follicular lymphoma) patients were treated with HDT and ASCT. Before ASCT, patients experienced a median of 2 disease phases (range, 1-4). After a median 5-year follow-up from ASCT, overall survival was 67% and EFS was 43%. When each of the 92 patients experiencing recurrence was taken as her/his own control, EFS was longer after ASCT than the duration of LQP (62%, P < .01). During LQP, 86 patients (93%) experienced recurrence in less than 5 years, compared with only 58 (63%) who experienced recurrence in the 5 years after ASCT (P < .01). CONCLUSION: HDT and ASCT can significantly increase EFS in comparison with the duration of the LQP for indolent lymphoma patients and can change disease course. This methodology has been found useful for evaluating new strategies, especially with monoclonal antibodies.     

Interim PET Response-adapted Strategy in Untreated Advanced Stage Hodgkin Lymphoma: Results of GOELAMS LH 2007 Phase 2 Multicentric Trial

Background

Patients with advanced stage Hodgkin lymphoma still present unsatisfactory outcomes.

Skin involvement in scleroderma--where histological and clinical scores meet

OBJECTIVES: A clinico-pathological study in diffuse systemic sclerosis (SSc) patients was performed to analyse whether the skin histological organization and the pro-fibrotic signals elicited by TGF-beta in fibroblasts vary according to the modified Rodnan skin score (mRSS). METHODS: Twenty-seven SSc patients underwent 45 skin biopsies with simultaneous measure of mRSS before or after treatment by immunosuppressive drugs, with or without autologous peripheral haematopoietic stem cell transplantation (HSCT). RESULTS: Double-blind optic microscopy analysis of the biopsies standard extracellular matrix stains allowed to define three histological subgroups: 6 with grade 1 weak fibrosis, 30 with grade 2 moderate fibrosis and 9 with grade 3 severe fibrosis. A significant (P < 0.0001) was identified between the grades of fibrosis and the mRSS. In skin fibroblast cultures, Smad3 phosphorylation levels, as well as mRNA steady-state levels of two transforming growth factor (TGF)-beta/Smad3 targets, COL1A2 and PAI-1, increased in parallel with the mRSS. When compared with pre-transplant values the degree of fibrosis observed after HSCT in the papillary and in the reticular dermis decreased in parallel with the fall in mRSS (n = 5 consecutive patients with repeated biopsies). CONCLUSIONS: The histological extent of skin fibrosis correlates closely with the mRSS. Both parameters appeared to regress after HSCT. The extent of TGF-beta signalling activation in SSc skin fibroblasts appears to parallel the severity of disease.     

SDF1/CXCL12 (−801GA) polymorphism is a prognostic factor after treatment initiation in Waldenstrom macroglobulinemia

The interaction of the chemokine CXCL12 with CXCR4 regulates homing of tumoral cells in bone marrow in Waldenstrom macroglobulinemia (WM). We assessed the distribution and the clinical influence of the CXCL12 (?801GA) polymorphism using PCR RFLP in a series of 114 WM patients. CXCL12 (?801AA) genotype was more frequent in WM patients compared with control subjects (p = 0.01). On the other hand, CXCL12 (?801GG) patients had a shorter median survival after initiation of first line therapy than remaining patients (p = 0.01). In conclusion, the CXCL12 (?801GA) polymorphism may either be associated with a high incidence of WM or influence clinical outcome.     

Recovery, viability and clinical toxicity of thawed and washed haematopoietic progenitor cells: analysis of 952 autologous peripheral blood stem cell transplantations

Cryopreservation and thawing of haematopoietic stem cells are associated with cell loss and infusion-related toxicities. We analysed viability, total nucleated cell (TNC) and CD34+ cell recovery, and infusion-related toxicities of 952 thawed and washed products. Mean TNC and CD34+ viable cells recoveries were 55.9+/-18.6 and 98.0+/-36.5%, respectively. Mean cell viability was 68.25+/-18.9%. TNC recovery was correlated with viability but independent of the initial nucleated cell concentration. No difference in TNC recovery or viability was observed according to underlying diseases, except for myeloma, for which these variables were significantly lower (P<0.05). CD34+ cell recovery was not correlated with viability or CD34+ initial count and was similar for all diseases. Cryostorage duration was not associated with cell loss. Immediate adverse events occurred in 169 patients (19%) and were moderate (grade I or II) for the majority of patients. Clinical toxicity was associated with a higher infused cell number and the presence of clumps in infused bags. The washing procedure of cell products lead to a low rate of adverse events, but patients transplanted with high cell numbers or bags in which clumps were identified are predisposed to such complications.     

Combined ifosfamide, etoposide and oxalipatin chemotherapy, a low-toxicity regimen for first-relapsed or refractory Hodgkin lymphoma after ABVD/EBVP: a prospective monocentre study on 34 patients

Around 20% of Hodgkin lymphoma (HL) patients are refractory to first‐line therapy with ABVD (adriamycin–bleomycin–vinblastine–dacarbazine) or relapse after complete remission. Salvage regimens frequently have delayed courses or require dose‐reduction because of haemotoxicity. We evaluated the IVOx (ifosfamide–etoposide–oxaliplatin) salvage regimen in terms of response rate, toxicity and stem‐cell mobilization. Thirty‐four patients with relapsed/refractory HL after anthracycline‐containing chemotherapy prospectively received IVOx, consisting of ifosfamide (1500 mg/m² days 1–3), etoposide (150 mg/m² days 1–3) and oxaliplatin (130 mg/m² day 1). Patients <65 years old received high‐dose therapy followed by autologous stem‐cell transplantation (HDT–ASCT). Response was assessed by computed and positron‐emission tomographies. Overall and complete response rates were 76% and 32%, respectively, after 2 cycles. Three episodes of febrile neutropenia occurred, and three patients required dose‐reductions. Twenty‐six patients underwent HDT–ASCT. With median follow‐up at 5 years, the 5‐year overall and event‐free survival rates were 74% and 63%, respectively. IVOx is a well‐tolerated outpatient regimen for relapsed HL, that does not hamper stem‐cell mobilization, achieves good response rates and compares favourably with previously published salvage regimens.     

Estimating late adverse events using competing risks after autologous stem-cell transplantation in aggressive non-Hodgkin lymphoma patients

BACKGROUND: Consolidative autologous stem-cell transplantation (ASCT) is a valuable option in high-risk or disease recurrence large-cell non-Hodgkin lymphoma patients (NHL); however, its long-term toxicity must still be assessed. METHODS: Among the 439 lymphoma patients transplanted at our institution from January 1, 1993, to January 1, 2002, 158 exhibited aggressive NHL. The median age of the patients was 46 years (range, 18-69), 98 males and 60 females. Ninety (57%) patients received first-line ASCT. The median number of prior chemotherapy regimens was 2 (range, 1-10). Thirty-eight (24%) patients received total body irradiation conditioning. Here we report the adverse events which occurred at least 30 days after ASCT and before disease recurrence. RESULTS: After a median follow-up of 3 years, the overall and disease-free survival rates were 61% and 55%, respectively. Sixty-eight late adverse events affected 43 (27%) patients, leading to a cumulative incidence of 34% at 3 years. Infections were the most frequent adverse events (n = 13), followed by neurologic (n = 12), pulmonary (n = 6), or cardiovascular (n = 4). Eight malignancies were diagnosed (six solid, two hematologic), leading to a cumulative incidence of 3.7% at 3 years. Taking into account the competing risks, multivariate analysis revealed that the number of progressions (relative risk [RR] = 2.68) and a mitoxantrone-containing conditioning regimen (RR = 2.98) significantly increased the incidence of late toxicity. CONCLUSION: ASCT is effective in patients with aggressive NHL with a poor prognosis. However, careful long-term follow-up of survivors is recommended because of the increase in malignant and nonmalignant toxicities.