The allogeneic dilemma

Harousseau, J-L

doi:10.1038/sj.bmt.1705810

Cited by 19 publications

(12 citation statements)

References 45 publications

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“…47 Whether an allograft should be offered as part of first-line treatment plan or as salvage therapy for refractory or relapsed patients is a matter of debate. 48 Although allografting with reduced intensity/nonmyeloablative conditionings has evolved into a less toxic procedure, new methods to further reduce toxicity while maintaining graft-versus-myeloma effects are being investigated. In our experience, the use of low-dose TBI conditioning regimens up-front proved significantly more effective in terms of graft-versusmyeloma effects than waiting with transplantation until relapse.…”

Section: Discussionmentioning

confidence: 99%

Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo

Bruno

Rotta

Patriarca

et al. 2009

Blood

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IntroductionDespite remarkable recent advances in its treatment, multiple myeloma remains incurable. 1 Allografting is still regarded as the only potential cure on account of its well-documented graft-versusmyeloma effect observed in a subset of patients. [2][3][4][5] However, its use remains controversial especially in newly diagnosed patients.In the late 1990s, the introduction of reduced intensity/ nonmyeloablative conditionings greatly renewed the interest in allografting, in particular for diseases such as myeloma where the transplantation-related mortality (TRM) with conventional transplantation regimens had been unacceptably high. [5][6][7] Combining the cytoreductive effect of a high-dose melphalan-based autograft with the graft-versus-myeloma effects of a nonmyeloablative allograft reduced TRM even in elderly, medically unfit myeloma patients. 8,9 Our recent comparison between autografting and nonmyeloablative allografting showed that the latter resulted in longer overall survival (OS) and event-free survival (EFS) in newly diagnosed patients younger than 65 years. 10 Preliminary reports from other groups have confirmed our findings. 11,12 Here, we report on an extended experience consisting of 100 newly diagnosed myeloma patients enrolled in a prospective clinical trial (http://ClinicalTrial.gov; NCT-00702247) and treated with nonmyeloablative allografts as part of their first-line treatment at 15 Italian Bone Marrow Transplantation Units of the Gruppo Italiano Trapianti di Midollo Osseo (GITMO). Methods Patients and donorsFrom July 1999 to June 2005, 100 newly diagnosed myeloma patients younger than 65 years were enrolled in a prospective multicenter trial. Informed consent was obtained upon enrollment in accordance with the An Inside Blood analysis of this article appears at the front of this issue.The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked ''advertisement'' in accordance with 18 USC section 1734. Inclusion criteria included diagnosis of untreated Durie & Salmon stage IIA to IIIB multiple myeloma or stage I progressed to require therapy; age less than 65 years; Karnofsky performance status greater than 60%; and presence of an human leukocyte antigen (HLA)-identical sibling donor eligible for peripheral blood stem cell (PBSC) donation. Exclusion criteria included prior treatment for myeloma, abnormal cardiac function and chronic respiratory disease defined as systolic ejection fraction less than 35% and carbon monoxide diffusing capacity less than 40% of predicted or need of continuous supplemental oxygen, respectively; serum bilirubins greater than twice normal and alanine amino transferase (ALAT) and/or aspartate amino transferase (ASAT) greater than 4 times normal; poorly controlled hypertension; pregnancy; and seropositivity for HIV. Patients with active nonhematologic malignancies except nonmelanoma skin cancers or who were less than 5 years from the achievement of complete remissi...

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Section: Discussionmentioning

confidence: 99%

Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo

Bruno

Rotta

Patriarca

et al. 2009

Blood

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“…There are two types of HSCT, autologous (patients receive their own, previously-harvested HSCs) and allogeneic (patients receive HSCs harvested from a related or unrelated donor). For autologous HSCT, patients receive high-dose chemotherapy and mean time to engraftment and the duration of neutropenia and mucositis may differ from those of allogeneic transplant recipients (1,2) . For allogeneic HSCT, patients also undergo conditioning regimens that combine high-dose chemotherapy and total body irradiation to induce immunosuppression.…”

Section: Introductionmentioning

confidence: 99%

Clinical impact of systematic nutritional care in adults submitted to allogeneic hematopoietic stem cell transplantation

Sommacal¹,

Gazal²,

Jochims³

et al. 2012

Revista Brasileira De Hematologia E Hemoterapia

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Background: The development of nutrition care programs for patients undergoing hematopoietic stem cell transplantation is necessity in view of the rapid and aggressive consequences frequently seen with this procedure. Patients require constant care to reduce complications and to contribute to the success of therapy. Methods: In an attempt to ascertain the impact of systematic nutritional care on patients submitted to allogeneic hematopoietic stem cell transplantation, the present study assessed the nutritional and clinical status, use of parenteral nutrition, and complication and mortality rates in two groups of patients, who were submitted to transplantation between April 2003 and December 2004 (Non-intervention Group - NIG; n = 57) and between March 2006 and January 2008 (Intervention Group - IG; n = 34). Results: There were no significant differences between groups in terms of clinical or nutritional profiles. Additionally, the length of hospital stay and complication and mortality rates were similar for both groups. However, time on parenteral nutrition during treatment was shorter for the IG [median 6.5 days (range: 1-28) for related donor recipients and 11 days (range: 1-21) for unrelated donor recipients] than for the NIG [median 20.5 days (range, 4-73) for patients submitted to myeloablative conditioning and 18.5 days (range: 11-59 days) for those submitted to nonablative conditioning]. Conclusion: The implementation of a nutritional follow-up and therapy protocol for adult patients submitted to hematopoietic stem cell transplantation shortens the duration of parenteral nutrition. It certainly has an impact on hospitalization costs and, potentially, on the rate of complications, even though this was not demonstrated in this study.

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“…Therefore, allogeneic BMT after myeloablative conditioning is abandoned by a large majority of investigators. 47 Much of the clinical impact of allogeneic SCT has been attributed to the immunologic effect of donor lymphoid cells which is called graft-versus-myeloma (GVM). This antitumor effect of donor immunocompetent cells, which is unfortunately linked to graft-versus host disease (GVHD), is the basis of reduced intensity conditioning (RIC) allogeneic SCT.…”

Section: Allogeneic Stem Cell Transplantationmentioning

confidence: 99%

Integrating Novel Therapies in the Transplant Paradigm

Harousseau¹

2009

The Cancer Journal

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The introduction of novel therapies (thalidomide, bortezomib, and lenalidomide) is changing the management of multiple myeloma in younger patients who are usually candidates for autologous stem cell transplantation (ASCT). Randomized trials have shown the superiority of induction treatment with novel agents compared with the classic VAD regimen. Complete remission plus very good partial remission rates of 40% to 60% after induction and of 60% to 75% are achieved with bortezomib-dexamethasone or with 3-drug combinations (including 1 or 2 novel agents). Six randomized studies have evaluated the impact of thalidomide as post-ASCT maintenance therapy. Despite differences in the design of the studies and in thalidomide administration, all 6 studies show a significant benefit in the thalidomide arm in terms of response rate and progression-free survival. Results are not as clear in terms of survival. The addition of novel agents before and after ASCT yields very high complete remission and promising progression-free survival rates. On the other hand, results obtained with novel agents are attractive as well and randomized studies comparing novel agents plus early ASCT versus novel agents plus ASCT at progression are planned.

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The allogeneic dilemma

Cited by 19 publications

References 45 publications

Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo

Nonmyeloablative allografting for newly diagnosed multiple myeloma: the experience of the Gruppo Italiano Trapianti di Midollo

Clinical impact of systematic nutritional care in adults submitted to allogeneic hematopoietic stem cell transplantation

Integrating Novel Therapies in the Transplant Paradigm

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