ERRATUM TO: Long-Term Tumor-Free Survival in a Patient with Stage IV Epithelial Ovarian Cancer Undergoing High-Dose Chemotherapy and Viscum album Extract Treatment: A Case Report es of Impairment and Severity

Abstract Many new therapeutic agents have been approved for follicular lymphoma (FL) but none appear to be curative. Despite novel agents, some patients (pts) experience early relapse, become chemorefractory or suffer transformation into more aggressive lymphomas. Options for these pts are limited. High dose chemotherapy with autologous stem transplant (ASCT) prolongs progression free survival (PFS) and overall survival (OS) in FL pts in first relapse and registry data shows favorable outcome with ASCT in cases of histologic transformation. However, ASCT is usually not curative. Myeloablative allogeneic transplant (MT) has produced long term PFS but is hampered by significant non relapse mortality (NRM) while nonmyeloablative transplant (NMT) has a higher relapse rate compared to MT especially in high risk pts. Finally, many transplant studies have excluded these high risk pts such as those with chemorefractory or transformed disease. We hypothesized that a tandem transplant consisting of an ASCT followed by a NMT would confer the same benefit as a MT without the associated high NRM by separating the high dose chemotherapy from graft versus host disease (GVHD) while preserving the graft versus lymphoma effect. The goal of our study was to improve long term PFS in high risk FL pts. We therefore initiated a prospective protocol in April 2003, for pts with high risk relapsed FL as defined by chemorefractory disease, early 1st relapse, >1st relapse or transformation into aggressive histology. At least one therapy was attempted to document chemosensitivity prior to ASCT. However, regardless of disease status prior to transplant, pts underwent ASCT followed 3 months later by an outpatient NMT from an HLA-identical sibling. NMT comprised 5 days of fludarabine 30 mg/m2/day and cyclophosphamide 300mg/m2/day followed by an infusion of >2x106CD34+ cells/kg. GVHD prophylaxis, chosen to take advantage of the low incidence of acute (a) GVHD and the putative protective effect of chronic (c) GVHD, consisted of tacrolimus starting on day (D) - 8 to achieve levels of 8-12 nmol/L then tapered off by D+100 or D+180 depending on disease risk and of mycophenolate mofetil 1g bid from D+2 to D+50. We previously reported on 27 pts with a follow-up (f/u) of 3 years (yrs). We now report a larger cohort of 40 pts with a median f/u of 8 yrs. Up until July 2015, 40 pts were enrolled with a median age of 50 yrs (34-65). Pts had previously been treated with a median of 3 lines of therapy (2-6). Median time from diagnosis to ASCT was 33 months. Disease status at ASCT was: 14 CR, 16 PR and 10 refractory. Conditioning for ASCT included BEAM/BEAC (n=39), and Cy-TBI (n=1). In addition, 4 pts received radiotherapy after ASCT to sites of previously bulky disease. Median time between ASCT and NMT was 138 days (75-238). Pre NMT disease status was: 25 CR, 12 PR and 3 refractory. Engraftment was prompt in all pts after ASCT and median neutrophil and platelet recovery were respectively 13 days (0-19) and 0 day (0-18) post NMT. Seven pts (18%) developed aGVHD: 2 grade II and 5 grade III. Overall, 29 pts (73%) developed cGVHD: 1 mild, 13 moderate and 15 severe according to NIH revised criteria. Median time to discontinuation of immunosuppression was 22 months. To date, 2 pts have progressed at 11 and 59 months post NMT (one died from relapse and one is now in CR after chemotherapy and DLI) and 5 pts died from either GVHD related complications (n=4) or unknown cause (n=1). All pts alive at last f/u were in CR. With a median f/u of 8 yrs in surviving pts (1-12), OS is 95% at 3 and 5 yrs and 82% at 8 yrs. PFS is 92% at 3yrs, 89% at 5 yrs and 80% at 8 yrs. NRM and relapse rate at 8 yrs are 18% and 6% respectively. Based on our current results in 40 pts, we conclude that ASCT followed by sibling NMT for high risk relapsed FL is associated with excellent disease response and PFS. Furthermore, this tandem strategy appears to be safe and well tolerated. The incidence of cGVHD remains high but could in part explain the impressive PFS in this high risk cohort. This approach should now be further explored in a multi institution setting, include matched unrelated donors and consider the addition of rituximab post-transplant to reduce the incidence and severity of cGVHD with the hope that relapse will not be increased. Figure 1 Figure 1. Disclosures Busque: Pfizer: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.

Download Full-text

Salvage Therapy of Progressive and Recurrent Hodgkin’s Disease: Results from a Multicenter Study of the Pediatric DAL/GPOH HD-Study Group.

Blood ◽

10.1182/blood.v104.11.612.612 ◽

2004 ◽

Vol 104 (11) ◽

pp. 612-612

Author(s):

Guenther Schellong ◽

Wolfgang Doerffel ◽

Alexander Claviez ◽

Dieter Koerholz ◽

Georg Mann ◽

...

Keyword(s):

Salvage Therapy ◽

Hodgkin's Disease ◽

Hodgkin’S Disease ◽

Disease Free Survival ◽

High Dose Chemotherapy ◽

High Dose ◽

Term Survival ◽

Free Survival ◽

First Relapse

Abstract To evaluate the efficacy of a salvage therapy (ST-HD-86) developed for children and adolescents with progressive or relapsed Hodgkin’s disease (HD) who were primarily treated in the pediatric DAL/GPOH studies. The essential chemotherapeutic elements were ifosfamide, etoposide, prednisone (IEP) and doxorubicine, bleomycin, vinblastine, dacarbazine (ABVD). 176 patients with progression (N=51) or first relapse (N=125) were enrolled by 67 centers from six countries between 1986 and 2003. The median time from initial diagnosis to progression/relapse was 1.1 (range, 0.02–17.1) years and the median patients age at the diagnosis of progression/relapse was 14.7 (range, 4.3–24.5) years. Salvage therapy consisted of 3–5 alternating cycles of IEP and ABVD, supplemented in part by 1–2 cycles of cyclophosphamide, vincristine, procarbazine, prednisone (COPP) or CCNU, etoposide, prednimustine (CEP). Radiotherapy was given to involved areas using individualized dosages. In the 1990ies, high-dose high dose chemotherapy with stem cell support was introduced for patients with unfavorable prognostic criteria. Disease-free survival (DFS) and overall survival (OS) at 10 years after initiation of salvage therapy are 63±4% and 74±4%. Second events occurred in 70 of 176 pts (40%). Risk factor analysis revealed the time until progression/relapse as the most discriminating prognostic factor (p=.0001). Patients with progression had an inferior outcome (DFS 41±7%, OS 51±8%), whereas patients with late relapses (>12 months after end of therapy) do very well (DFS 87±4%, OS 90±4%). The result of study ST-HD-86 with a long-term survival of 74% in this large cohort of patients with progressive or relapsed HD can be considered favorable. While the salvage strategy for patients with progression has to be further optimized, a reduction of intensity might be considered for those patients with late relapses following HD in childhood or adolescence.

Download Full-text

A Single Institution Long-Term Experience Using Autologous Stem Cell Transplantation for the Management of Hodgkin’s Lymphoma.

Blood ◽

10.1182/blood.v104.11.5233.5233 ◽

2004 ◽

Vol 104 (11) ◽

pp. 5233-5233

Author(s):

Barry S. Skikne ◽

Narotham Thudi ◽

Delva Deauna-Limayo ◽

Siddhartha Ganguly ◽

David Bodensteiner ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Salvage Therapy ◽

High Dose Chemotherapy ◽

High Dose ◽

Free Survival ◽

Primary Induction ◽

Induction Failure

Abstract Patients with stage III – IV Hodgkin’s lymphoma (HL), and those with bulky stage I/II disease have a disease relapse rate of 30–40% after primary treatment. High dose chemotherapy with stem cell transplantation is a treatment option after relapse or in those with primary induction failure. In the present study, we retrospectively examined long term outcomes in 45 relapsed/primary induction failure HL patients undergoing autologous peripheral stem cell (25 patients), bone marrow (17 patients) or combination (3 patients) transplantation between 1985 and December 2003. The median age was 32 yrs(16–64), 38 had Nodular Sclerosing HL, 17 patients had stage I/II, 13 stage III and 15 stage IV disease, and 33 had B symptoms at diagnosis. Twenty patients were previously treated with 1–2 prior regimens, while 25 had ≥3 treatment regimens. Sixteen patients had sensitive disease to salvage therapy given prior to transplantation, 27 had resistance to salvage therapy while 2 did not undergo salvage therapy prior to transplantation. Five patients had primary resistant disease, 33 had evidence of relapsed disease and 7 patients were in CR at the time of transplantation. CBV was used in 30 patients, BEAM in 9 patients and 5 patients received CY/TBI based regimens. Six patients (13%) had early mortality (< 100 days) directly attributable to the procedure. Four of these deaths were cardiac related and two were due to infection. The overall response was 93% with CR achieved in 28 (62%) and incomplete response in 14 (31%). The median overall survival (OS) was 5.5 yrs, the median disease free survival (DFS) was 1 yr with DFS at 5 yrs of 26%. For patients achieving a CR after transplantation, 67% remain alive at a median of 7 yrs from transplant, however, the median progression free survival in these patients was 3.7yrs. For 15 patients not achieving CR after transplantation, 3(20%) have survived, the median time to death in this group was 20 months. Seventeen patients are alive, 2 are lost to follow-up and 21 patients have died. Fourteen patients died from disease progression (31%), 2 (4%) died from MDS/AML occurring after 32 and 66 mnths, 2 died of late occurring infections, 2 related to respiratory failure and a further patient from late cardiac failure. OS and DFS did not differ between peripheral stem cell vs bone marrow transplantation, those with B symptoms at diagnosis, sex differences, age <20yrs vs >20yrs, high dose therapy regimens but a difference in OS (p=0.04) and DFS (p=0.03) was seen in patients transplanted in CR vs active disease at transplantation. Patients whose disease displayed sensitivity to salvage therapy immediately prior to transplant did show a trend towards improved OS and DFS, but this was not statistrically significant. High dose chemotherapy and autologous stem cell transplantation can be expected to lead to long term DFS in approximately 25–35% of patients. Cardiac mortality (11%) appears to be a higher than expected complication in this patient group.

Download Full-text