Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumors

Blaise, Didier; Bay, Jacques Olivier; Faucher, Catherine; Michallet, Mauricette; Boiron, Jean‐Michel; Choufi, Bachra; Cahn, Jean‐Yves; Gratecos, N; Sotto, Jean‐Jacques; François, Sylvie; Fleury, J; Mohty, Mohamad; Chabannon, Christian; Bilger, Karin; Gravis, Gwénaëlle; Viret, F.; Braud, Anne Chantal; Bardou, Valérie‐Jeanne; Maraninchi, D; Viens, Patrice

doi:10.1182/blood-2003-07-2236

Cited by 118 publications

(76 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The GvL effect represents a widely accepted major component of allogeneic stem cell transplantation, 6 and there is emerging evidence also for a graft versus tumor effect in solid tumors. [7][8][9] Over the last three decades, experience on allogeneic transplantation in pediatric patients with rhabdomyosarcoma and EWS has been collected. Most patients were transplanted from matched related or matched unrelated donors.…”

Section: Introductionmentioning

confidence: 99%

Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing’s sarcoma patients

Schlegel

Feuchtinger

Nitschke-Gérard

et al. 2015

Bone Marrow Transplant

View full text Add to dashboard Cite

Natural killer (NK) cell activity has been shown to have potential activity against Ewing's sarcoma (EWS) especially in tumors with low HLA I expression and high NKG2D expression. Two patients with metastatic relapsed and primary metastatic stage IV EWS who had received two courses of high dose chemotherapy with autologous stem cell rescue were transplanted from a haploidentical parental stem cell donor. Patients are alive in ongoing CR for 10.2 and 3.4 years now. Post transplant local second and first relapses were treated successfully in both patients. In vivo IL-2 stimulation not only increased the number and activity of effector cells in one patient but was also associated with severe GvHD. In vitro studies demonstrated high NK cell activity against K562 and relevant activity against EWS cell line A673 post transplant. NK activity was enhanced by cytokine prestimulation as well as by EWS targeting anti-GD2 Ab. Haploidentical hematopoietic stem cell transplantation (HSCT) might contribute to long-term survival by NK cellmediated effect exerted by donor-derived NK cells. Local tumor recurrence was manageable in both high-risk patients indicating systemic immune control preventing subsequent metastasizing. The efficacy of haploidentical HSCT, cytokine application and tumor targeting antibodies for the use of Ab-dependent cellular cytotoxicity needs evaluation in clinical trials.

show abstract

Section: Introductionmentioning

confidence: 99%

Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing’s sarcoma patients

Schlegel

Feuchtinger

Nitschke-Gérard

et al. 2015

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…This correlation was already observed in previous studies. 18,[23][24][25] Similarly, Nelson recently established that OC induces a host immune response involving T-cells, which prolong OS. 26 Unfortunately, this observation was not confirmed by comparison of times to progression between cGvHD and nonecGvHD patients, which was not significant.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic hematopoietic stem cell transplantation in ovarian cancer—the EBMT experience

Bay¹,

Cabrespine-Faugeras²,

Tabrizi³

et al. 2010

Intl Journal of Cancer

View full text Add to dashboard Cite

Although preliminary results suggest that allogeneic hematopoietic stem cell transplantation (allo HCT) for ovarian cancer (OC) is a feasible procedure, the low patient number in previous studies had limited ability to evaluate the true benefit of allo HCT in OC. This retrospective multicenter study included 30 patients with OC allografted between 1995 and 2005 to determine the outcome of patients with OC treated with allo HCT. Prior to allo HCT, patients were in complete response (n 5 1), partial response (n 5 7), stable disease (n 5 11) or had progressive disease (n 5 13). An objective response (OR) was observed in 50% (95% CI, 33-67) of patients. Three patients of responding patients had an objective response following the development of acute graft-versus-host disease (aGvHD). The cumulative incidence of chronic GvHD (cGVHD) was 34% (95% CI, 18-50). Transplant relative mortality rates were 7 and 20% on day 100 and 1 year, respectively. With a median follow-up of 74.5 months (range 16-148), median progression free survival (PFS) was 6 months and median overall survival (OS) was 10.4 months. Patients who developed cGvHD following allo HCT had a significant OS improvement compared to those who did not (17.6 months vs. 6.5 months, p 5 0.042). However, PFS was not similarly significantly improved in patients who developed cGvHD (12 months versus 3.7 months, p 5 0.81). Allo HCT in OC may lead to graft-versus-OC effects. Their clinical relevance remains to be shown.Ovarian cancer (OC), the fifth-leading cause of death for women in the United States and Europe, is the most deadly of the gynecologic malignancies. 1 Current systemic therapy consists of a combination of carboplatin and paclitaxel. Even after extensive surgery and chemotherapy, up to 50% of patients suffer from relapsing disease. Median overall survival (OS) for patients after recurrence is $2 years. 2 To improve outcome, high-dose chemotherapy regimens have been tried usually based on carboplatin combinations. These appear to delay relapse but have no influence on OS. [3][4][5] Allogeneic hematopoietic stem cell transplantation (allo HCT) is an effective therapy for many hematological malignancies. The therapeutic benefit of allogeneic transplantation relies not only on high-dose chemotherapy administered before transplantation but also is largely related to an immune-mediated graft-versus-leukemia effect, due to transplantation of the donor's immune system along with the hematopoietic tissue. Recent data from experimental animal models and from preliminary clinical experience suggest that a graft-versus-tumor effect, analogous to the graft-versusleukemia effect, may be generated against solid tumors such as renal cell cancer, breast cancer and OC. 6 Regarding OC, immunotherapy agents such as systemic or intraperitoneal interleukin-2 7-9 and adoptive transfer of tumor-infiltrating lymphocytes 10 have been used with success, testifying to the

show abstract

“…1,2 It ultimately uses a lower dose conditioning regimen and can thus be offered to older patients, to those debilitated by additional comorbidities, or to high-risk, heavily pretreated patients, who would not tolerate myeloablative HCT, resulting in a consequent decrease in regimen-related toxicity and treatment-related mortality. [3][4][5] Acute kidney injury (AKI) is highly prevalent whether the patients undergo myeloablative or non-myeloablative regimens; however, the pathogenesis and risk factors leading to AKI can differ between the two. In fact, AKI in patients receiving HCT is associated not only with increased short-and long-term mortality as compared with patients with no AKI, but also with a higher rate of progression to chronic kidney disease (CKD).…”

Section: Introductionmentioning

confidence: 99%

Acute kidney injury in HCT: an update

Lopes

Jorge

Neves

2016

Bone Marrow Transplant

View full text Add to dashboard Cite

Acute kidney injury (AKI) is highly prevalent whether the patients undergo myeloablative or non-myeloablative hematopoietic cell transplantation (HCT); however, the pathogenesis and risk factors leading to AKI can differ between the two. The prognosis of AKI in patients receiving HCT is poor. In fact, AKI following HCT is associated not only with increased short-and long-term mortality, but also with progression to chronic kidney disease. Herein, the authors provide a comprehensive and up-to-date review of the definition and diagnosis, as well as of the incidence, pathogenesis and outcome of AKI in patients undergoing HCT, centering on the differences between myeloablative and non-myeloablative regimens. INTRODUCTIONHematopoietic cell transplantation (HCT) is currently used to treat numerous malignant (for example, multiple myeloma, leukemias and lymphomas) and non-malignant hematological disorders (for example, aplastic anemia, b-thalassemia, immunodeficiency disorders and inborn errors of metabolism), as well as solid tumors (for example, breast cancer and neuroblastoma), which are in other instances incurable.The two major HCT procedures, taking into consideration the conditioning regimen used, are myeloablative autologous and allogeneic HCT and non-myeloablative allogeneic HCT. On the one hand, myeloablative HCT utilizes the maximally tolerated dose of TBI with or without chemotherapy, or with chemotherapy alone. On the other hand, non-myeloablative HCT depends more on donor cellular immune effects and less on the cytotoxic effects of the preparative regimen to control the underlying disease. 1,2 It ultimately uses a lower dose conditioning regimen and can thus be offered to older patients, to those debilitated by additional comorbidities, or to high-risk, heavily pretreated patients, who would not tolerate myeloablative HCT, resulting in a consequent decrease in regimen-related toxicity and treatment-related mortality. [3][4][5] Acute kidney injury (AKI) is highly prevalent whether the patients undergo myeloablative or non-myeloablative regimens; however, the pathogenesis and risk factors leading to AKI can differ between the two. In fact, AKI in patients receiving HCT is associated not only with increased short-and long-term mortality as compared with patients with no AKI, but also with a higher rate of progression to chronic kidney disease (CKD). Herein, the authors provide a comprehensive and up-to-date review of the definition and diagnosis of AKI as well as of the incidence, risk factors, pathogenesis and outcome of AKI in patients undergoing HCT, centering on the differences between myeloablative and nonmyeloablative regimens.

show abstract

Reduced-intensity preparative regimen and allogeneic stem cell transplantation for advanced solid tumors

Cited by 118 publications

References 32 publications

Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing’s sarcoma patients

Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing’s sarcoma patients

Allogeneic hematopoietic stem cell transplantation in ovarian cancer—the EBMT experience

Acute kidney injury in HCT: an update

Contact Info

Product

Resources

About