(Tra)pianti (Italian Edition)

This was grade 4 in 3 patients. Overall, 53 of 85 patients, 27 of 73, and 10 of 36 remained on immunosuppression at 1, 2, and 4 years after allografting, respectively. One patient in CR with severe bronchiolitis obliterans successfully underwent lung transplantation. Overall TRM was By the intention-to-treat principle, after a median follow-up of 5 years range, 0.

Among the 96 patients who completed the program, after a median follow-up of 5 years range, 2. No differences in both the updated OS and EFS between the previously reported cohort of 52 patients 10 and the newly described 44 were observed HR 0. Furthermore, the probability of a patient being alive in first remission or in a subsequent remission due to salvage therapy is illustrated in Figure 3. There was no significant difference in median OS between the 2 cohorts of patients not reached versus 4. Ig indicates immunoglobulin; and HCT, hematopoietic cell transplantation.

A OS between patients without del 13 q solid line; median not reached and patients with del 13 q dotted line; median 4. B EFS between patients without del 13 q solid line; median 4. Progress in myeloma treatment has been impressive in the past 10 years with the introduction of high-dose melphalan followed by autologous transplantation and, recently, through the identification of new agents with molecular targets such as thalidomide, lenalidomide, and bortezomib.

Conversely, in the light of a well-documented graft-versus-myeloma effect, allografting may be curative in a subset of patients.

First, the high transplantation-related toxicity associated with myeloablative conditionings has severely limited its application; second, the retrospective nature of several studies with strong patient selection bias and the lack of large prospective controlled trials have not allowed definitive conclusions. This strategy meant that they were all treated uniformly and any statistical bias was greatly reduced.

By contrast, prospective studies, which include allografting as part of the up-front treatment regardless of the induction therapy, inevitably result in bias that may highly affect the clinical outcomes. In the present study, median OS was not reached after a follow-up of 5 years.

Ladetto, Division of Hematology, S.

Storie di trapianti per la vita

Giovanni Battista Hospital, University of Torino, Torino, Italy, oral communication, November , prelude to a cure, with a follow-up extending to 8 years. Thus, the depth of response was crucial for prolonged response in our study Table 3. Graft-versus-myeloma effects and the new drugs with molecular targets, in fact, are by no means mutually exclusive.

Bortezomib and thalidomide have already been shown to reinduce remissions in patients who relapsed after allografting. We are currently investigating the role of lenalidomide in reducing the tumor burden before and enhancing graft-versus-myeloma effect after transplantation. Maintenance therapy may lead to a significant increase in response rates and prolonged response duration. Furthermore, this strategy may also overcome the higher risk of relapse in patients with poor prognostic factors. Its incidence, however, may be further reduced as progress is made in the understanding of its pathogenesis.

In a subset of patients, therefore, a graft-versus-myeloma effect may be distinct from detrimental chronic GVHD or associated with subclinical graft-versus-host reactions.

Resta in contatto

Evaluation of their number in a larger series of patients may help to set a range that allows consistent donor engraftment while reducing the risk of acute GVHD. It is widely assumed that chromosomal abnormalities are important prognostic factors for both OS and EFS. In the present series, del 13 appeared to significantly affect EFS 4. The data reported in all these studies should, however, be evaluated with larger and more comprehensive analyses that include a complete spectrum of the chromosomal abnormalities associated with myeloma rather than a single abnormality.

Recent reports clearly showed that del 13 alone did not affect OS after transplantation unless it was associated with other abnormalities such as del 17 or t 4; 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. In our experience, the use of low-dose TBI conditioning regimens up-front proved significantly more effective in terms of graft-versus-myeloma effects than waiting with transplantation until relapse.

These might be due to an antigen expression profile of potential targets for allogeneic cytotoxic T cells that progressively changed. There was a significantly higher incidence of CR and a longer progression-free survival in patients treated with an allograft. The authors concluded that, although the progression-free survival plateau was encouraging, the procedure should be investigated in prospective clinical trials.

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In summary, our findings suggested that allografting was effective in the treatment of newly diagnosed myeloma patients. Our thanks to the nurses and medical staff for caring for the patients, to the study coordinators who collected the trial and follow-up data, and to Antonio Capaldi, Giovannino Ciccone, Paolo Di Bartolomeo, Michele Falda, Andrea R. Sandmaier, and Barry E. Storer for their contributions to the manuscript. 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.

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Sorasio contributed patients to the study, verified data, and assisted in drafting the manuscript; F. Storb contributed to study design and reviewed the manuscript; I. The authors declare no competing financial interests. National Center for Biotechnology Information , U. Prepublished online Dec 8.

Author information Article notes Copyright and License information Disclaimer. Received Jul 17; Accepted Nov This article has been cited by other articles in PMC. Abstract Despite recent advances, allografting remains the only potential cure for myeloma. Introduction Despite remarkable recent advances in its treatment, multiple myeloma remains incurable.

Methods Patients and donors From July to June , newly diagnosed myeloma patients younger than 65 years were enrolled in a prospective multicenter trial. Nonmyeloablative allografting Upon recovery from autografting, defined as resolved mucositis, no evidence of cytomegalovirus CMV reactivation or disease, and no need for intravenous medications, planned range of 2 to 4 months, patients were conditioned for allografting with a single dose of nonmyeloablative cGy total body irradiation TBI on day 0.

Analyses of chimerism Chimerism analyses of peripheral blood T cells, granulocytes, and unfractionated marrow were carried out at days 28, 56, , after allografting and every 6 months thereafter or as clinically indicated with fluorescence in situ hybridization FISH in sex-mismatched pairs or polymerase chain reaction PCR —based analyses of polymorphic microsatellite regions in sex-matched pairs as previously described. Chromosomal abnormalities Chromosome 13q deletion [del 13 ] was analyzed by interphase FISH techniques on freshly purified bone marrow plasma cells as previously described.

Supportive care and GVHD grading After allografting, all patients received standard prophylaxis against bacterial and fungal infections; herpes simplex and varicella-zoster virus reactivation; and Pneumocystis carinii. Disease response Response was evaluated before each treatment, monthly for the first 6 months after allografting and at least every 3 months thereafter or as clinically indicated. Statistical analysis Primary end points of the study were OS and EFS from diagnosis according to the intention-to-treat principle and in patients who completed the program.

Results Patients Patient characteristics are shown in Table 1. Characteristic Patients enrolled, no. Open in a separate window. Engraftment and response Ninety-six allografts were carried out at a median of 90 range days after the autograft.

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Salvage therapy Thirty-six patients were treated for disease relapse and 6 for progression of stable disease. Transplantation-related toxicity Thirty-six patients developed grade 2 to 4 acute GVHD at a median of 41 range, days. Outcome By the intention-to-treat principle, after a median follow-up of 5 years range, 0. Discussion Progress in myeloma treatment has been impressive in the past 10 years with the introduction of high-dose melphalan followed by autologous transplantation and, recently, through the identification of new agents with molecular targets such as thalidomide, lenalidomide, and bortezomib.

Acknowledgments Our thanks to the nurses and medical staff for caring for the patients, to the study coordinators who collected the trial and follow-up data, and to Antonio Capaldi, Giovannino Ciccone, Paolo Di Bartolomeo, Michele Falda, Andrea R. Footnotes An Inside Blood analysis of this article appears at the front of this issue. Allogeneic transplantation for multiple myeloma: Standard chemotherapy compared with high-dose chemoradiotherapy for multiple myeloma: Allogeneic marrow transplantation for multiple myeloma: Progress in allogenic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: Autologous stem cell transplantation followed by a dose-reduced allograft induces high complete remission rate in multiple myeloma.

Allografting with nonmyeloablative conditioning following cytoreductive autografts for the treatment of patients with multiple myeloma. A comparison of allografting with autografting for newly-diagnosed myeloma. N Engl J Med. I am an independent science journalist, my English-language site became world-wide the most extensive resource for the Paolo Macchiarini affair in regenerative medicine. Briefly, these were his victims: You might have heard about this scandal, where human patients were experimented upon using artificial tracheas, most are now dead, the rare survivors were left mutilated.

Especially Corriere Fiorentino covered the Italian side of the scandal, namely the journalist Alessio Gaggioli, for example:. You will notice that 5 patients were operated with trachea transplants in Italy, at the Ospedale Careggi in Florence, where Macchiarini used to be in charge of thoracic surgery. One patient was British, one Czech, three Italian. All are dead now, though one might have survived with permanent brain damage.

We do not know what happened to her by now, or if there were more patients. Furthermore, the very first patient who received a trachea transplant from Macchiarini, Claudia Castillo, was treated post-operatively at Careggi. The results were published in in a dishonest publication in the most prestigious journal The Lancet, the work originated from Careggi. Afterwards, Careggi helped Macchiarini cover up the events and the fates of these patients, no investigation ever happened.

The Italian health authorities were misled and lied to by Careggi clinicians.

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The trachea transplant affair in Italy is actually far from over, even with Macchiarini gone. Birchall also apparently referred the aforementioned British patient to Macchiarini to be operated at Careggi, who soon afterwards suffered a very slow and horrible death. This means that Italian patients will be recruited and receive potentially lethal trachea transplants in Brescia. Up to 48 patients are scheduled, and Italy will become the main trial site, since the scheduled site in Vienna, Austria abandoned the consortium, and the doctors responsible for the trial site in Warsaw, Poland expressed their worries about the dangers of this technology to me in an email.

In Sweden, the Macchiarini affair is still under investigation, massive misconduct and patient abuse breaching the Nuremberg Codex of were already established. In Iceland, an investigation was launched to follow-up the death of the patient Andemariam Beyene whom Macchiarini operated with a plastic trachea in Sweden.

In UK, the parliament now began investigating trachea transplants performed by Macchiarini and Birchall, while paying a special attention to the trial Tetra. Only in Italy, nothing much seems to happen in this regard, the Centro Nazionale Trapianti is seemingly clueless, while both Careggi and Brescia responsibles refused to answer any questions. Hence I am wondering if you would be inclined to promote a parliamentarian investigation into the Italian side of the Macchiarini affair. Or several of small tips, just increase the amount as you like.

Your generous patronage of my journalism, however small it appears to you, will greatly help me with my legal costs. Like Liked by 1 person. In Italia, lo scandalo Macchiarini continua — OggiScienza.

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