The clinical features, management and prognostic effects of pathological fractures in a multicenter series of 373 patients with diffuse large B-cell lymphoma of the bone.

BACKGROUND: Pathological fractures (PFs) occur in 10%-20% of patients with diffuse large B-cell lymphoma (DLBCL) of the bone. The clinical features and the effects of this severe complication on management and prognosis have not been previously analyzed in a large series. PATIENTS AND METHODS: The effects of PF on management and prognosis were reviewed in an international retrospective series of 373 patients with newly diagnosed bone DLBCL, comparing 78 patients with PF at presentation (group 'PF-BL') and 295 patients without PF ('controls'). RESULTS: At a median follow-up of 53 months (range 3-246), PF-BL patients exhibited lower rates of overall response (ORR, 78% versus 85%; P = 0.17), 5-year progression-free survival (PFS, 53 ± 6% versus 61 ± 3%; P = 0.02) and 5-year overall survival (OS, 54 ± 6% versus 68 ± 3%, P = 0.008) than controls. Initial surgical stabilization of the PF did not change therapeutic outcome (5-year OS: 45 ± 9% versus 54 ± 10%; P = 0.20). PF-BL patients referred to irradiation of the fractured bone before chemotherapy exhibited a significantly poorer outcome than patients managed with the inverse sequence (ORR: 52% versus 92%, P = 0.0005; 5-year OS: 22 ± 14% versus 64 ± 9%, P = 0.007). Multivariate analysis confirmed the independent association between PF and worse survival and the negative effect of radiotherapy as initial therapy. CONCLUSION: Fracture is an independent, adverse prognostic event in patients with bone DLBCL. Anthracycline-based chemotherapy followed by radiotherapy seems to be the better treatment sequence. Initial fracture stabilization does not seem to improve outcome; it should be used to improve patient's quality of life only if chemotherapy delays can be avoided.

Tandem autologous stem cell transplantation in multiple myeloma after high-dose chemotherapy with two separate collections: single institution experience.

Presented is a retrospective analysis of multiple myeloma patients transplanted at our institution between November 1993 and August 2007. The objective of this analysis was to assess the feasibility and toxicity of tandem autologous stem cell transplantation (T-ASCT) when stem cells were harvested before first and before second transplantation separately. A total of 90 patients transplanted in our center were analyzed, of whom 43 patients were in tandem transplantation group.The overall response rate (ORR) was 83.7% and 95.1%, estimated five-year overall survival (OS) was 40.1% and 60.0%, probability of five-year event-free survival (EFS) was 18.2% and 25.6%, transplant related mortality (TRM) was 6.3% and 4.6% in the single and tandem transplant group, respectively. In multivariable analysis of all 90 patients, tandem transplantation and ORR attained after induction therapy were favourable prognostic factors for OS (p=0.024 and p=0.002) and EFS (p=0.036 and p=0.008), respectively. In conclusion, tandem transplantation with two separate stem cell harvests, performed separately before the each transplantation, is feasible in majority of patients with acceptable toxicity.

Autologous stem cell transplantation with selected CD34+ cells and unmanipulated peripheral blood stem cells in patients with relapsed and refractory Hodgkin's lymphoma: a single centre experience.

With the aim to evaluate the long term outcome after high-dose chemotherapy and autologous stem cell transplantation (HDCT+ASCT) in patients with relapsed or refractory Hodgkin's lymphoma (HL) we performed a retrospective analysis of patients transplanted at our centre. Between January 1993 and December 2005, 126 consecutive patients with relapsed or refractory HL in the age of 16 to 65 years underwent HDCT+ASCT at our centre and were enrolled in this retrospective analysis. Patients were autografted with either CD34+ positively selected or unmanipulated periferal blood stem cells (PBSC). With a median follow up of 69 months (3-162 months), the actuarial 5-y PFS and OS for all patients after HDCT+ASCT were 59% and 72%, respectively. In patients transplanted from 1996 the actuarial 5-y PFS and OS for CD34+ selected group were 64% and 79% and for unmanipulated PBSC group 63% and 66%, respectively. A total of 42/126 (33%) patients died. Treatment related mortality (TRM) was 3% (4 patients). In univariate analysis, chemosensitive disease and increased LDH were the strongest prognostic factors for PFS and OS. Our results confirm the efficacy of HDCT+ASCT in relapsed or refractory HL with acceptable toxicity. The use of CD34+ positively selected stem cells for autografting is feasible, safe and effective procedure.

BEACOPP and COPP/ABVD as salvage treatment after primary extended field radiation therapy of early stage Hodgkins disease - results of the German Hodgkin Study Group.

Patients with early stage favorable Hodgkin's disease who relapse after extended field radiotherapy have satisfactory results. We retrospectively analysed patients with relapsed HD after initial radiation therapy alone to determine treatment outcome and prognostic factors. Nine-hundred and forty five patients in localized stages without risk factors received either 40 Gy extended field RT or 30 Gy EF RT followed by an additional 10 Gy to involved lymph node regions. 107 patients relapsed and received salvage therapy. Characteristics of the 107 patients at relapse were as follows: median age was 34 years (range 18--75) with relapse occuring at a median of 19 months (range 4--98 months), 31% were female. The majority of patients (93%) were treated with conventional chemotherapy. Sixty-nine percent were treated with COPP/ABVD like regimens, 21% with BEACOPP, and 3% received various other regimens. Seven percent were treated with radiotherapy alone. Complete remission was achieved in 87% of all salvaged patients. The median follow-up after relapse was 45 months. FF2F (freedom from second treatment failure) and OS (overall survival) were 81% and 89%, respectively. In multivariate analysis age was the major prognostic factor for FF2F and OS (p<0.0001, for both). Further independent prognostic factors were B symptoms (p=0.05) and salvage chemotherapy (p=0.03) for FF2F, and B symptoms (p=0.03) and extranodal involvement (p=0.02) for OS. The long-term outcome of patients relapsing after EF RT is excellent. Age, B symptoms, extranodal involvement and salvage chemotherapy were identified as prognostic factors for second relapse and survival.

A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin's disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly).

In contrast to younger patients, the prognosis of elderly patients with advanced Hodgkin's disease (HD) has not improved substantially over the last 20 years. We thus carried out a prospectively randomized study (HD9(elderly)) to compare the BEACOPP regimen in this setting against standard COPP-ABVD. Between February 1993 and 1998, 75 patients aged 66-75 years with newly diagnosed HD in advanced stages were recruited into the HD9 trial as a separate stratum (HD9(elderly)). Patients were assigned to eight alternating cycles of COPP and ABVD or eight cycles of BEACOPP in baseline doses. Radiotherapy was given to initial bulky or residual disease. In total, 68 of 75 registered patients were assessable: 26 were treated with COPP-ABVD and 42 with BEACOPP baseline. There were no significant differences between COPP-ABVD and BEACOPP in terms of complete remission (76%), overall survival (50%) and freedom from treatment failure (FFTF) (46%) at 5 years. At a median follow-up of 80 months, a total of 37 patients died: 14/26 patients (54%) treated with COPP-ABVD and 23/42 patients (55%) with BEACOPP. Two patients (8%) treated with COPP-ABVD and nine patients (21%) treated with BEACOPP died of acute toxicity. Hodgkin-specific FFTF at 5 years was 55% after COPP-ABVD and 74% after BEACOPP (P=0.13). Thus, there are no differences in survival between these regimens in elderly patients.

Use of selected CD34+ cells in the treatment of relapsed/progressive HD: experiences from a single center.

BACKGROUND: Treatment of HD using positively selected stem cells can achieve a durable CR in almost 80% patients, with a median follow-up of 24 months. We have found the use of positive selected CD34+ cells in the treatment of relapsed/progressive HD after high-dose chemotherapy to be a safe procedure with promising results. METHODS: Positively selected (CD34+) stem cells were employed for autografting in the patients with HD after high-dose chemotherapy. RESULTS: Between April 1996 and February 2001, 28 patients with relapsed/progressive HD were autografted with positively selected CD34+ cells at our Institute. All patients are alive and we did not observe any deaths as a result of toxicity. From this group, 22 (78.6%) patients are in durable CR, with a median follow-up of 24 months (range 7-65 months). Six (21.4%) patients relapsed but are now in CR after radiotherapy and mini-allogeneic transplantation (one patient) or radiotherapy (five patients). DISCUSSION: Autologous transplantation with positively selected CD34+ cells in relapsed HD is a safe and effective procedure in the treatment of this disease.