Stromal damage as consequence of high-dose chemo/radiotherapy in bone marrow transplant recipients

Galotto, Maria; Berisso, Giovanni; Delfino, Laura; Podestà, Marina; Ottaggio, Laura; Dallorso, Sandro; Dufour, Carlo; Ferrara, Giovanni Battista; Abbondandolo, Angelo; Dini, Giorgio; Bacigalupo, Andrea; Cancedda, Ranieri; Quarto, Rodolfo

doi:10.1016/s0301-472x(99)00076-4

Cited by 253 publications

(193 citation statements)

References 33 publications

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“…It is possible that in AMeL patients, transplantation procedures could cause a more relevant damage of the marrow stromal microenvironment, as already reported in patients undergoing BMT. 28 This hypothesis could find support in the data concerning postchemotherapy aplasia, which is seen to last longer than expected.…”

Section: Discussionmentioning

confidence: 68%

Acute megakaryoblastic leukemia: experience of GIMEMA trials

et al. 2002

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The objective of the study was to evaluate the incidence, characteristics, treatment and outcome of acute megakaryoblastic leukemia (AMeL) in patients enrolled in GIMEMA trials. Between 1982 and 1999, 3603 new consecutive cases of AML aged over 15 years were admitted to GIMEMA trials. Of them, 24 were AMeL. The incidence of AMeL among AML patients enrolled in GIMEMA trials was 0.6% (24/3603). Diagnosis was based on morphological criteria. Out of 11 cytogenetic studies performed two presented chromosome 3 abnormalities. Twelve patients (50%) reached a CR, five (21%) died in induction and seven (27%) were unresponsive. The median duration of CR was 35 weeks (range 10-441). Seven patients underwent transplantation procedures (1 BMT, 4 aBMT, 2 aPBSCT). Four patients died in CR due to chemotherapy-related complications. Comparing the CR rate between AMeL and the other cases of AML enrolled in GIMEMA trials, no differences were observed. These results were mirrored for different age groups. The median survival was 40 weeks. At present, after a followup of a minimum of 2 years, only two patients are alive in CR, all the others having died. A 5-year Kaplan-Meier curve shows a disease-free survival of 17% and an actuarial overall survival of 10%. AMeL is a rare form of AML. The CR duration and the overall survival in this group of patients are very poor, even if similar to those observed in other AML. Furthermore, a high number of deaths in CR were observed. On the basis of these data, a specific therapeutic approach, possibly with innovative treatments, should be evaluated.

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Section: Discussionmentioning

confidence: 68%

Acute megakaryoblastic leukemia: experience of GIMEMA trials

et al. 2002

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“…35 These effects have been reported for different members of the bisphosphonate family, including zoledronic acid, pamidronate, neridronate, alendronate and risedronate. 34,40,41 In a previous study, we documented that bone effects of zoledronic acid in transplanted patients were associated with a significant improvement in the regenerating capacity of osteogenic stromal lineage precursors. Similar findings have also been reported for risedronate in vitro: risedronate stimulated osteoblast proliferation in a human trabecular bone culture model.…”

Section: Discussionmentioning

confidence: 96%

“…40 The positive effects on osteoblasts may be particularly important in allo-transplanted patients, since previous evidence indicated a persistently reduced regenerative and functional capacity of osteoblast precursors. 3,23,24,41,42 Although we did not evaluate osteoblastic lineage behavior in patients treated by risedronate, it is likely that BMD improvement produced by risedronate is at least in part related to its anabolic effects, in analogy with what we documented with zoledronic acid. 13 As a matter of fact, the improvement observed in the patients treated by bisphosphonates was highly significant at both LS and FN.…”

Section: Discussionmentioning

confidence: 96%

Effects of various antireabsorptive treatments on bone mineral density in hypogonadal young women after allogeneic stem cell transplantation

Tauchmanovà

Simone

Musella

et al. 2005

Bone Marrow Transplant

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“…Studies have also demonstrated that a recipient's stromal cells are damaged after bone marrow transplantation [10,11,13] or even from chemotherapeutic drugs alone [6,8].…”

Section: Discussionmentioning

confidence: 99%

“…Various studies to date have evaluated the toxic effects of HDC and demonstrated severe and irreversible damage on mature bone marrow stromal compartments in vivo and in vitro [5][6][7][8][9][10][11][12][13][14]. These effects are relevant not only in patients treated with HDC without allogeneic stem cells but also in recipients of allogeneic stem cell transplants in whom bone marrow stroma remains recipient in origin after the transplant [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy

et al. 2010

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Hematopoietic recovery after high-dose chemotherapy (HDC) in the treatment of hematological diseases may be slow and/or incomplete. This is generally attributed to progressive hematopoietic stem cell failure, although defective hematopoiesis may be in part due to poor stromal function. Chemotherapy is known to damage mature bone marrow stromal cells in vitro, but the extent to which marrow mesenchymal stem cells (MSCs) are damaged by HDC in vivo is largely unknown. To address this question, the phenotype and functional properties of marrow MSCs derived from untreated and chemotherapeutically treated patients with hematological malignancy were compared. This study demonstrates a significant reduction in MSC expansion and MSC CD44 expression by MSCs derived from patients receiving HDC regimens, thus implicating potential disadvantages in the use of autologous MSCs in chemotherapeutically pretreated patients for future therapeutic strategies. The clinical importance of these HDCinduced defects we have observed could be determined through prospective randomized trials of the effects of MSC cotransplantation on hematopoietic recovery in the setting of HDC with and without hematopoietic stem cell rescue.

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Stromal damage as consequence of high-dose chemo/radiotherapy in bone marrow transplant recipients

Cited by 253 publications

References 33 publications

Acute megakaryoblastic leukemia: experience of GIMEMA trials

Acute megakaryoblastic leukemia: experience of GIMEMA trials

Effects of various antireabsorptive treatments on bone mineral density in hypogonadal young women after allogeneic stem cell transplantation

Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy

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