45 results on '"di Grazia, C."'
Search Results
2. Assessment of orbital volume and morphological changes after rapid maxillary expansion performed with tooth-bone and bone-borne devices. A retrospective study using surface-to surface matching technique
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Nicotra, C, Ronsivalle, V, Casella, F, Di Grazia, C, Isola, G, and Lo Giudice, A
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- 2020
3. S1624 A DAY 100 LAB-SCORE PREDICTS EXTENSIVE CGVHD, OVERALL SURVIVAL AND TRANSPLANT-RELATED MORTALITY AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION: FINAL ANALYSIS
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Metafuni, E., primary, Cavattoni, I., additional, Lamparellli, T., additional, Raiola, A.M., additional, Ghiso, A., additional, Galaverna, F., additional, Gualandi, F., additional, Di Grazia, C., additional, Dominietto, A., additional, Varaldo, R., additional, Van Lint, M.T., additional, Angelucci, E., additional, and Bacigalupo, A., additional
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- 2019
- Full Text
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4. Prophylactic antithymocyte globulin reduces the risk of chronic graft-versus-host disease in alternative-donor bone marrow transplants
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Bacigalupo, A, Lamparelli, T, Gualandi, F, Bregante, S, M. Raiola, A, Di Grazia, C, Dominietto, A, Bruno, B, Galbusera, V, Frassoni, F, Podesta, M, Tedone, E, Occhini, D, and Van Lint, M.T
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- 2002
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5. Small bowel intussussception due to metastatic melanoma of unknown primary site. Case report
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STAGNITTI, F., ORSINI, S., MARTELLUCCI, A., TUDISCO, A., AVALLONE, M., AIUTI, F., DI GIROLAMO, V., STEFANELLI, F., DE ANGELIS, F., COSTANTINO, A., DI GRAZIA, C., NAPOLEONI, A., NICODEMI, S., CIPRIANI, B., CECI, F., MOSILLO, R., CORELLI, S., CASCIARO, G., and SPAZIANI, E.
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Male ,Oncology ,Pathology ,medicine.medical_specialty ,Ileum ,Metastasis ,Clinical Practice ,Internal medicine ,medicine ,Humans ,Malignant melanoma ,Unknown primary ,Intestinal intussusceptions ,Disseminated disease ,Melanoma ,Gastrointestinal tract ,business.industry ,Middle Aged ,medicine.disease ,Ileal Neoplasms ,medicine.anatomical_structure ,Iron-deficiency anemia ,Neoplasms, Unknown Primary ,Segmental resection ,business ,Intestinal Obstruction ,Brain metastasis - Abstract
Malignant melanoma is characterized by metastases also to the gastrointestinal tract, especially in the small bowel. The diagnosis is often delayed because unspecific clinical presentation (frequently as chronic iron deficiency anemia, rectal bleeding or intestinal obstruction). We present a case of melanoma of unknown primary site, with clinical presentation of intestinal obstruction. A segmental resection of the ileum was performed including mesentery with lymph nodes. Histology revealed metastatic melanoma from unknown primary. PET and MRI confirmed disseminated disease without brain metastasis.
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- 2014
6. Biliodigestive fistulae and gallstone ileus;diagnostic and therapeutic considerations. Our experience
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F. Stefanelli, Spaziani E, A. Costantino, Andrea Napoleoni, Tudisco A, S. Nicodemi, De Angelis F, Di Grazia C, Ceci F, Orsini S, M. Avallone, B. Cipriani, Di Girolamo, F. Aiuti, Franco Stagnitti, Corelli S, Mosillo R, Martellucci A, and G E Casciaro
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Past medical history ,medicine.medical_specialty ,business.industry ,Fistula ,medicine.medical_treatment ,General surgery ,fistulae ,gallstone ,Context (language use) ,medicine.disease ,Bowel obstruction ,Gallstone ileus ,Cholecystitis ,medicine ,ileus ,Cholecystectomy ,business ,Complication - Abstract
The biliodigestive fistula is not a rare affection in the context of acute pathology of the gastrointestinal tract. It often affects patients between 63 and 85 years old , particularly the female sex, and the most common cause is acute or chronic cholecystolithiasis. Open issues are the delayed in the pre-operative diagnosis, and controversies exist regarding the best surgical approach. The choice of treatment options is influenced by the age of the patients and their clinical conditions and also by the presence of comorbidities and of a delayed right diagnosis. In the 1 to 3% of cases, the biliodigestive fistula presents a gallstone ileus as complication, whose diagnosis is particularly difficult for the lack of specific signs and symptoms. The contrast-enhanced CT is considered the gold standard for a specific pre-operative diagnosis, as it directly shows the fistula. Surgical treatments include one-stage procedure or two-stage procedure. Many studies seem to favor a deferred definitive procedure. The Authors describe 4 cases: in 3 cases, women between 70 and 80 years old presenting an history of recurrent cholecystitis, in 2 cases, and in 1 case presenting a bowel obstruction; in 1 case a 50-years-old man, with no significant past medical history, presenting a bowel obstruction. The Authors have performed in the 2 cases of gallstone ileus an enterolithotomy with cholecysto-duodenal fistula repair and cholecystectomy, in one-stage, and this has been possible because of the good clinical conditions of the patients and their low operative risk. In the case of fistula without the complication of gallstone ileus, the treatment approach has been cholecysto-gastric fistula closure with a gastroplastic using separate stitches and cholecystectomy, in one-stage. We are in agreement with data in the literature regarding the delay into the diagnosis of biliodigestive fistula and with the importance to suspect it or gallstone ileus presence, although the clinical presentation is extremely non-specific. In our experience, cholangiopancreatography-CT and CECT have made easier the pre-operative diagnosis and so reducing the delay of the treatment.
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- 2014
7. Risk management in surgery
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Messano, GIUSEPPE ALESSIO, Spaziani, Erasmo, Turchetta, F., Ceci, F., Corelli, S., Casciaro, Giovanni Enrico, Martellucci, A., Costantino, A., Napoleoni, A., Cipriani, B., Nicodemi, S., Di Grazia, C., Mosillo, R., Avallone, M., Orsini, S., Tudisco, A., Aiuti, F., and Stagnitti, Franco
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antibiotic therapy ,laparoscopic drainage ,liver abscesses ,percutaneous drainage ,risk management ,Risk Management ,Italy ,Surgical Procedures, Operative ,Humans ,Focus on ,Checklist - Abstract
Malpractice is the responsible for the greatest number of legal claims. At the present time, legal actions against physicians in Italy are 15,000 per year, and a stunning increase about costs to refund patients injured by therapeutic and diagnostic errors is expected. The method for the medical prevention is “Risk Management”, that is the setting-up of organizational instruments, methods and actions that enable the measurement or estimation of medical risk; it allows to develop strategies to govern and reduce medical error. In the present work, the reconstruction about the history of risk management in Italy was carried out. After then the latest initiatives undertaken by Italy about the issue of risk management were examined.
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- 2013
8. Leukemia Relapse after Allogeneic Transplants in AML: Predictive Role of WT1 Expression and Protective Effect of DLI.
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Bacigalupo, Andrea, primary, Dominietto, A., additional, Di Grazia, C., additional, Pozzi, S., additional, Bertolotti, F., additional, Podesta’, M., additional, Lamparelli, T., additional, Gualandi, F., additional, Ibatici, I., additional, Bregante, S., additional, Pinto, V., additional, and Frassoni, F., additional
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- 2008
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9. 224: Thiotepa based conditioning regimen in 374 patients undergoing allogeneic stem cell transplants from related or unrelated donors
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Bacigalupo, A., primary, Gualandi, F., additional, Occhini, D., additional, Bregante, S., additional, Lamparelli, T., additional, Raiola, A.M., additional, Ibatici, A., additional, Di Grazia, C., additional, Dominietto, A., additional, Bruno, B., additional, van Lint, M.T., additional, and Frassoni, F., additional
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- 2007
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10. Reducing transplant-related mortality after allogeneic hematopoietic stem cell transplantation
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Bacigalupo, A., Sormani, M. P., Lamparelli, T., Gualandi, F., Occhini, D., Bregante, S., ANNA MARIA RAIOLA, Di Grazia, C., Dominietto, A., Tedone, E., Piaggio, G., Podesta, M., Bruno, B., Oneto, R., Lombardi, A., Frassoni, F., Rolla, D., Rollandi, G., Viscoli, C., Ferro, C., Garbarino, L., and Lint, M. T.
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Adult ,Male ,Neutropenia ,Transplantation Conditioning ,Multiple Organ Failure ,Premedication ,Graft vs Host Disease ,Infections ,Anti-Infective Agents ,Actuarial Analysis ,Cause of Death ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Transplantation, Homologous ,Bone Marrow Transplantation ,Retrospective Studies ,Salvage Therapy ,Infection Control ,Peripheral Blood Stem Cell Transplantation ,Leukemia ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,Combined Modality Therapy ,Survival Analysis ,Treatment Outcome ,Hematologic Neoplasms ,Female ,Lung Diseases, Interstitial ,Immunosuppressive Agents - Abstract
Transplant-related mortality (TRM) following allogeneic hematopoietic stem cell transplantation (HSCT) has been reported to be related to disease stage, duratiion of disease and type of donor. Furthermore, the outcome of transplants performed in the 1990s appears to be better than that of transplants done in the previous decade. The aims of this study were to determine whether these relationships still hold and whether the outcome of transplants is continuing to improve.We analyzed 1180 consecutive patients with leukemia (n=979) or other hematologic malignancies (n=201) undergoing HSCT in 4 time periods: before 1990, 1991-1995, 1996-2000, and 2001-2002. Changes during these eras include increasing patient age, more unrelated transplants, more patients with advanced disease, different graft-versus-host disease (GvHD) prophylaxis, and different management of infections.The actuarial 2-year transplant-related mortality (TRM) differed significantly between the transplant eras (p0.001) with a significant interaction with disease phase (p=0.018). In patients in first remission (n=585) TRM was 34%, 25%, 21% and 6% in the four transplant eras. The reduction in TRM was less evident in patients in second remission (n=284) (37%, 35%, 30%, 25%) and absent in relapsed patients (n=311) (TRM=45%, 41%, 29%, 51%). This is a consequence of reductions in GvHD, infections and multiorgan failure among patients in remission but not among those who relapse. The actuarial 2-year survival has improved significantly in patients in first remission (54%, 66%, 72%, 78%) but not in those in second remission (38%, 46%, 52%,45%), or relapsed patients (31%, 25%, 36%, 21%).In conclusion, TRM has been significantly reduced in first remission patients, suggesting an allograft should be considered in this phase, when appropriate, without delay. There has been no improvement in survival for patients beyond first remission, due to persisting high risk of infections and organ toxicity, a possible consequence of prolonged pre-transplant chemotherapy and neutropenia.
11. Liver resection for hemoperitoneum caused by spontaneous rupture of unrecognized hepatocellular carcinoma
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giovanni casciaro, Spaziani, E., Costantino, A., Ceci, F., Di Grazia, C., Martellucci, A., Pecchia, M., Cipriani, B., Angelis, F., Corelli, S., Napoleoni, A., Stefanelli, F., Salvadori, C., Parisella, M., Nicodemi, S., and Stagnitti, F.
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Aged, 80 and over ,Male ,Carcinoma, Hepatocellular ,Rupture, Spontaneous ,Hemoperitoneum ,Liver Neoplasms ,Hepatectomy ,Humans - Abstract
Hepatocellular carcinoma (HCC) is an increasingly common form of cancer. Although its spontaneous rupture is rare in Western countries, it constitutes a surgical emergency and is associated with high mortality. There is a lack of consensus as to the best approach and what parameters to use in choosing it. The three main approaches are conservative, endovascular and resection - the treatment of choice for acute abdominal bleeding. We report a case of hemoperitoneum following the spontaneous rupture of an unrecognized HCV-related HCC in a patient with no history of liver disease. The patient was successfully treated by emergency surgery, with resection of two segments of the left liver.
12. Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes
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Elisabetta Sauta, Marie Robin, Matteo Bersanelli, Erica Travaglino, Manja Meggendorfer, Lin-Pierre Zhao, Juan Carlos Caballero Berrocal, Claudia Sala, Giulia Maggioni, Massimo Bernardi, Carmen Di Grazia, Luca Vago, Giulia Rivoli, Lorenza Borin, Saverio D'Amico, Cristina Astrid Tentori, Marta Ubezio, Alessia Campagna, Antonio Russo, Daniele Mannina, Luca Lanino, Patrizia Chiusolo, Luisa Giaccone, Maria Teresa Voso, Marta Riva, Esther Natalie Oliva, Matteo Zampini, Elena Riva, Olivier Nibourel, Marilena Bicchieri, Niccolo’ Bolli, Alessandro Rambaldi, Francesco Passamonti, Victor Savevski, Armando Santoro, Ulrich Germing, Shahram Kordasti, Valeria Santini, Maria Diez-Campelo, Guillermo Sanz, Francesc Sole, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Gastone Castellani, Matteo Giovanni Della Porta, Sauta, E, Robin, M, Bersanelli, M, Travaglino, E, Meggendorfer, M, Zhao, L, Caballero Berrocal, J, Sala, C, Maggioni, G, Bernardi, M, Di Grazia, C, Vago, L, Rivoli, G, Borin, L, D'Amico, S, Tentori, C, Ubezio, M, Campagna, A, Russo, A, Mannina, D, Lanino, L, Chiusolo, P, Giaccone, L, Voso, M, Riva, M, Oliva, E, Zampini, M, Riva, E, Nibourel, O, Bicchieri, M, Bolli, N, Rambaldi, A, Passamonti, F, Savevski, V, Santoro, A, Germing, U, Kordasti, S, Santini, V, Diez-Campelo, M, Sanz, G, Sole, F, Kern, W, Platzbecker, U, Ades, L, Fenaux, P, Haferlach, T, Castellani, G, and Della Porta, M
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Cancer Research ,Oncology ,Myelodysplastic Syndrome ,MDS ,IPSS-M ,Hematology ,Settore MED/15 - Abstract
PURPOSE Myelodysplastic syndromes (MDS) are heterogeneous myeloid neoplasms in which a risk-adapted treatment strategy is needed. Recently, a new clinical-molecular prognostic model, the Molecular International Prognostic Scoring System (IPSS-M) was proposed to improve the prediction of clinical outcome of the currently available tool (Revised International Prognostic Scoring System [IPSS-R]). We aimed to provide an extensive validation of IPSS-M. METHODS A total of 2,876 patients with primary MDS from the GenoMed4All consortium were retrospectively analyzed. RESULTS IPSS-M improved prognostic discrimination across all clinical end points with respect to IPSS-R (concordance was 0.81 v 0.74 for overall survival and 0.89 v 0.76 for leukemia-free survival, respectively). This was true even in those patients without detectable gene mutations. Compared with the IPSS-R based stratification, the IPSS-M risk group changed in 46% of patients (23.6% and 22.4% of subjects were upstaged and downstaged, respectively). In patients treated with hematopoietic stem cell transplantation (HSCT), IPSS-M significantly improved the prediction of the risk of disease relapse and the probability of post-transplantation survival versus IPSS-R (concordance was 0.76 v 0.60 for overall survival and 0.89 v 0.70 for probability of relapse, respectively). In high-risk patients treated with hypomethylating agents (HMA), IPSS-M failed to stratify individual probability of response; response duration and probability of survival were inversely related to IPSS-M risk. Finally, we tested the accuracy in predicting IPSS-M when molecular information was missed and we defined a minimum set of 15 relevant genes associated with high performance of the score. CONCLUSION IPSS-M improves MDS prognostication and might result in a more effective selection of candidates to HSCT. Additional factors other than gene mutations can be involved in determining HMA sensitivity. The definition of a minimum set of relevant genes may facilitate the clinical implementation of the score.
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- 2023
13. Treatment of steroid resistant acute graft versus host disease with an anti-CD26 monoclonal antibody-Begelomab
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Edoardo Benedetti, Carlo Borghero, Francesca Gualandi, Anna Paola Iori, Mattia Algeri, Carmen Di Grazia, Patrizia Chiusolo, Maurizio Musso, Carmine Selleri, Antonio M. Risitano, Anna Maria Raiola, Francesca Bonifazi, Massimo Martino, Alice Bertaina, Francesco Onida, Emanuele Angelucci, Alessandro Rambaldi, Riccardo Varaldo, Andrea Bacigalupo, Simona Sica, Franco Locatelli, Francesco Zallio, Fabio Ciceri, Lucia Prezioso, Matteo Parma, Bacigalupo, A., Angelucci, E., Raiola, A. M., Varaldo, R., Di Grazia, C., Gualandi, F., Benedetti, E., Risitano, A., Musso, M., Zallio, F., Ciceri, F., Chiusolo, P., Sica, S., Rambaldi, A., Bonifazi, F., Parma, M., Martino, M., Onida, F., Iori, A. P., Selleri, C., Borghero, C., Bertaina, A., Prezioso, L., Algeri, M., and Locatelli, F.
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Adult ,medicine.medical_specialty ,medicine.drug_class ,Graft vs Host Disease ,Monoclonal antibody ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Acute graft versus host disease ,medicine ,Humans ,Prospective Studies ,Treatment of steroid resistant acute graft versus ,Stage (cooking) ,Adverse effect ,Prospective cohort study ,Transplantation ,biology ,business.industry ,Hematopoietic Stem Cell Transplantation ,Compassionate Use ,Antibodies, Monoclonal ,Hematology ,Steroid resistant ,Settore MED/15 - MALATTIE DEL SANGUE ,begelomab ,methylprednisolone ,acute respiratory failure ,030220 oncology & carcinogenesis ,Acute Disease ,biology.protein ,Steroids ,Antibody ,business ,treatment of steroid resistant acute graft versus host disease with an anti cd26 monoclonal antibody begelomab ,030215 immunology - Abstract
We have treated 69 patients with steroid refractory acute graft versus host disease (SR-aGvHD), with an anti-CD26 monoclonal antibody (Begelomab): 28 patients in two prospective studies (EudraCT No. 2007-005809-21; EudraCT No. 2012-001353-19), and 41 patients on a compassionate use study. The median age of patients was 42 and 44 years; the severity of GvHD was as follows: grade II in 8 patients, grade III in 33, and grade IV in 28 patients. There were no adverse events directly attributable to the antibody. Day 28 response was 75% in the prospective studies and 61% in the compassionate use patients, with complete response rates of 11 and 12%. Response for grade III GvHD was 83 and 73% in the two groups; response in grade IV GvHD was 66 and 56% in the two groups. Non relapse mortality (NRM) at 6 months was 28 and 38%. Overall there were 64, 56, 68% responses for skin, liver, and gut stage 3-4 GvHD. The overall survival at 1 year was 50% for the prospective studies and 33% for the compassionate use patients. In conclusion, Begelomab induces over 60% responses in SR-aGvHD, including patients with severe gut and liver GvHD, having failed one or more lines of treatment.
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- 2020
14. Extracorporeal photopheresis for the treatment of steroid refractory acute GVHD
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Bénédicte Bruno, Stefania Bregante, Adalberto Ibatici, P Perfetti, P Stura, Almalina Bacigalupo, C. Di Grazia, Domenico Occhini, Teresa Lamparelli, P. Carlier, M. T. Van Lint, G M Ferrari, Francesca Gualandi, Enrico Pogliani, Alida Dominietto, Paolo Strada, A M Raiola, S Zia, Perfetti, P, Carlier, P, Strada, P, Gualandi, F, Occhini, D, Van Lint, M, Ibatici, A, Lamparelli, T, Bruno, B, Raiola, A, Dominietto, A, Di Grazia, C, Bregante, S, Zia, S, Ferrari, G, Stura, P, Pogliani, E, and Bacigalupo, A
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Male ,Adult ,medicine.medical_specialty ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,education ,Drug Resistance ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Gastroenterology ,Young Adult ,fluids and secretions ,Photopheresis ,Retrospective Studie ,Internal medicine ,Immunopathology ,Extracorporeal Photopheresis ,medicine ,Humans ,Steroid ,Survival rate ,Retrospective Studies ,Photopheresi ,Aged ,Immunosuppression Therapy ,Transplantation ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,medicine.disease ,Surgery ,Survival Rate ,Treatment Outcome ,Graft-versus-host disease ,Methylprednisolone ,Acute Disease ,Chronic Disease ,Steroids ,Female ,business ,Immunosuppression ,Human ,medicine.drug - Abstract
Extracorporeal photopheresis (ECP) was given to 23 patients with steroid-refractory acute GVHD (aGVHD, grade II (n=10), III (n=7) or IV (n=6)). The median duration of ECP was 7 months (1-33) and the median number of ECP cycles in each patient was 10. Twelve patients (52%) had complete responses. Eleven patients (48%) survived and 12 died, 10 of GVHD with or without infections and two of leukaemia relapse. The average grade of GVHD was reduced from 2.8 (on the first day of ECP) to 1.4 (on day +90 from ECP) (P=0.08), and the average dose of i.v. methylprednisolone from 2.17 to 0.2 mg/kg/d (P=0.004). Complete responses were obtained in 70, 42 and 0% of patients, respectively, with grades II, III and IV aGVHD; complete responses in the skin, liver and gut were 66, 27 and 40%. Patients treated within 35 days from onset of aGVHD had higher responses (83 vs 47%; P=0.1). A trend for improved survival was seen in grade III-IV aGVHD treated with ECP as compared to matched controls (38 vs 16%; P 0.08). ECP is a treatment option for patients with steroid refractory aGVHD and should be considered early in the course of the disease.
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- 2008
15. Busulfan-fludarabine versus busulfan-cyclophosphamide for allogeneic transplant in acute myeloid leukemia: long term analysis of GITMO AML-R2 trial.
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Cavallaro G, Grassi A, Pavoni C, Micò MC, Busca A, Cavattoni IM, Santarone S, Borghero C, Olivieri A, Milone G, Chiusolo P, Musto P, Saccardi R, Patriarca F, Pane F, Saporiti G, Rivela P, Terruzzi E, Cerretti R, Marotta G, Carella AM, Nagler A, Russo D, Corradini P, Bernasconi P, Iori AP, Castagna L, Mordini N, Oldani E, Di Grazia C, Bacigalupo A, and Rambaldi A
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- Humans, Middle Aged, Adult, Female, Male, Aged, Follow-Up Studies, Busulfan administration & dosage, Busulfan therapeutic use, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute drug therapy, Vidarabine analogs & derivatives, Vidarabine administration & dosage, Vidarabine therapeutic use, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Hematopoietic Stem Cell Transplantation methods, Transplantation Conditioning methods, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Transplantation, Homologous
- Abstract
We report the long-term results of a randomized trial (GITMO, AML-R2), comparing 1:1 the combination of busulfan and cyclophosphamide (BuCy2, n = 125) and the combination of busulfan and fludarabine (BuFlu, n = 127) as conditioning regimen in acute myeloid leukemia patients (median age 51 years, range 40-65) undergoing allogeneic hematopoietic stem cell transplantation. With a median follow-up of 6 years, significantly better non-relapse mortality (NRM) was confirmed in BuFlu recipients, which is sustained up to 4 years after transplant (10% vs. 20%, p = 0.0388). This difference was higher in patients older than 51 years (11% in BuFlu vs. 27% in BuCy2, p = 0.0262). The cumulative incidence of relapse, which was the first cause of death in the entire study population, did not differ between the two randomized arms. Similarly, the leukemia-free survival (LFS) and overall survival (OS) were not different in the two cohorts, even when stratifying patients per median age. Graft-and relapse-free survival (GRFS) in BuFlu arm vs. the BuCy2 arm was 25% vs. 20% at 4 years and 20% vs. 17% at 10 years. Hence, the benefit gained by NRM reduction is not offsets by an increased relapse. Leukemia relapse remains a major concern, urging the development of new therapeutic approaches., (© 2024. The Author(s).)
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- 2024
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16. Haploidentical bone marrow transplantation for AML in remission after TBF conditioning: a long-term follow-up.
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Raiola AM, Di Grazia C, Dominietto A, Bregante S, Giammarco S, Varaldo R, Sorà F, Metafuni E, Limongiello MA, Laudisi A, Passannante M, Galli E, Gambella M, Sica S, Bacigalupo A, Angelucci E, and Chiusolo P
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- Humans, Bone Marrow Transplantation, Follow-Up Studies, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy
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- 2024
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17. Acute graft versus host disease 1976-2020: reduced incidence and predictive factors.
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Di Francesco A, Raiola AM, Dominietto A, Di Grazia C, Gualandi F, Van Lint MT, Bregante S, Chiusolo P, Laurenti L, Sora F, Giammarco S, Metafuni E, Fresa A, Sica S, Angelucci E, and Bacigalupo A
- Abstract
We studied the incidence of acute graft versus host disease (GvHD) and its outcome in three consecutive time frames (year <2000; 2000-2010; >2010), in 3,120 patients allografted in two transplant Centers between 1976 and 2020. The median age increased over the three periods from 32 to 42 to 54 years ( p < 0.00001). The median day of onset of GvHD in the three periods was day +14, day +16, and day +30, respectively ( p < 0.0001). The cumulative incidence (CI) of GvHD grades II-IV in the three periods was 47, 24, and 16%, respectively ( p < 0.00001). The CI of GvHD grades III-IV was 13, 5, and 4% ( p < 0.001). In multivariate analysis, significant predictive factors for GvHD II-IV, on top of year of transplant, were anti-thymocyte globulin (ATG) (RR 0.67, p > 0.001); post-transplant cyclophosphamide (PTCY) (RR 0.41, p < 0.001), a family mismatched donor (RR 1.31, p = 0.03) a matched unrelated donor (RR 2.1, p < 0.001), an unrelated mismatched donor (RR1.8, p = 0.001), donor age above 40 years (RR 1.27, p < 0.001), hematological malignancy-as compared to aplastic anemia (RR 2.3, p < 0.001). When selecting only GvHD grade II, in a multivariate analysis, there was a significant reduction of transplant-related mortality (TRM) for patients grafted in 2001-2010 (RR 0.62, p < 0.0001) and for patients grafted in 2011-2020 (RR 0.35, p < 0.0001) as compared to grafts before the year 2000. A similar reduction in time was seen for patients with GvHD grades III-IV. The overall TRM in the three periods was 30, 22, and 16% ( p < 0.0001) and survival was 47, 51, and 58% ( p < 0.0001). Relapse risk was unchanged. In conclusion, we showed improved prevention of acute GvHD with time, together with a significant delay in the onset of the disease. Treatment of GvHD has also improved over time, as suggested by both reduced TRM and improved survival in more recent transplant periods., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Di Francesco, Raiola, Dominietto, Di Grazia, Gualandi, Van Lint, Bregante, Chiusolo, Laurenti, Sora, Giammarco, Metafuni, Fresa, Sica, Angelucci and Bacigalupo.)
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- 2024
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18. Total Marrow Irradiation for Second Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Advanced Acute Leukemia.
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Dominietto A, Vagge S, di Grazia C, Bregante S, Raiola AM, Varaldo R, Gualandi F, Gusinu M, Barra S, Agostinelli S, Angelucci E, and Hui S
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- Humans, Young Adult, Adult, Middle Aged, Aged, Retrospective Studies, Bone Marrow, Melphalan, Thiotepa, Acute Disease, Recurrence, Leukemia, Myeloid, Acute radiotherapy, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease prevention & control
- Abstract
Second allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment option for patients with acute leukemia who relapse after a first HSCT. Although myeloablative conditioning (MAC) regimens before the first HSCT are considered superior to reduced- intensity conditioning (RIC) in terms of disease control in acute leukemia patients, the optimal conditioning regimen for the second allogeneic HSCT remains controversial. The most important prognostic factors are the remission disease phase at the time of the second HSCT and an interval >12 months from the first HSCT to the second HSCT. Total marrow irradiation (TMI) is an advanced high-precision radiation treatment that delivers therapeutic doses over extensively selected targets while substantially reducing radiation to vital organs compared to conventional total body irradiation (TBI). Here we report the results of a retrospective analysis of second allogeneic HSCT treated with TMI as an MAC regimen with the intent of limiting toxicity. We investigated the efficacy of high dose per fraction TMI in combination with thiotepa, fludarabine, and melphalan in 13 consecutive patients with acute leukemia who had relapsed after a first allogeneic HSCT treated between March 2018 and November 2021. Donor type was haploidentical in 10 patients, unrelated in 2 patients, and HLA-identical sibling in 1 patient. The conditioning regimen consisted of 8 Gy TMI in 5 patients on days -8 and -7 and 12 Gy TMI in 8 patients on days -9 to -7, plus thiotepa 5 mg/kg on day -6, fludarabine 50 mg/day on days -5 to -3, and melphalan 140 mg/day on day -2. The TMI was delivered at the dosage og 4 GY for 2 consecutive days (total = 8 GY) or for 3 consecutive days (total = 12 GY). The median patient age was 45 years (range, 19 to 70 years); 7 patients were in remission, and 6 had active disease at the time of their second allogeneic HSCT. The median time to a neutrophil count of >.5 × 10
9 /L was 16 days (range, 13 to 22 days), and the median time to a platelet count of >20 × 109 /L was 20 days (range, 14 to 34 days). All patients showed complete donor chimerism on day +30 post-transplantation. The cumulative incidence of grade I-II acute graft-versus-host disease (GVHD) was 43%, and that of chronic GVHD was 30%. The median duration of follow-up was 1121 days (range, 200 to 1540 days). Day +30 and +100 transplantation-related mortality (TRM) was 0. The overall cumulative incidence of TRM, relapse rate, and disease free-survival were 27%, 7%, and 67%, respectively. This retrospective study demonstrates the safety and efficacy of a hypofractionated TMI conditioning regimen in patients with acute leukemia undergoing second HSCT with encouraging outcomes in terms of engraftment, early toxicity, GVHD, and relapse., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. All rights reserved.)- Published
- 2023
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19. Comparison of outcomes for HLA-matched sibling and haplo-identical donors in Myelodysplastic syndromes: report from the chronic malignancies working party of EBMT.
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Raj K, Eikema DJ, Sheth V, Koster L, de Wreede LC, Blaise D, Di Grazia C, Koc Y, Potter V, Chevallier P, Lopez-Corral L, Wu D, Mielke S, Maertens J, Meijer E, Huynh A, Passweg J, Luft T, Pérez-Simón JA, Ciceri F, Piekarska A, Hayri Ozsan G, Kröger N, Robin M, and Yakoub-Agha I
- Subjects
- Adult, Cyclophosphamide therapeutic use, Humans, Middle Aged, Recurrence, Retrospective Studies, Siblings, Transplantation Conditioning, Unrelated Donors, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation, Myelodysplastic Syndromes drug therapy, Neoplasms drug therapy
- Abstract
Myelodysplastic syndromes (MDS) are the second common indication for an Allo-HCT. We compared the outcomes of 1414 matched sibling (MSD) with 415 haplo-identical donors (HD) transplanted with post-transplant cyclophosphamide (PTCy) as GVHD prophylaxis between 2014 and 2017. The median age at transplant with MSD was 58 and 61 years for HD. The median time to neutrophil engraftment was longer for HD being 20 vs 16 days for MSD (p < 0.001). Two-year overall survival (OS) and PFS (progression free survival) with MSD were significantly better at 58% compared with 50%, p ≤ 0.001, and 51% vs 47%, p = 0.029, with a HD. Relapse at 2 years was lower with a HD 23% than with MSD 29% (p = 0.016). Non relapse mortality (NRM) was higher with HD in the first 6 months post-transplant [HR 2.59 (1.5-4.48) p < 0.001] and was also higher at 2 years being 30% for HD and 20% for MSD, p ≤ 0.001. The incidence of acute GVHD grade II-IV and III-IV at 100 days was comparable for MSD and HD, however, chronic GVHD at 2 years was significantly higher with MSD being 44% vs 32% for HD (p < 0.001). After multivariable analysis, OS and primary graft failure were significantly worse for HD particularly before 6 months [HR 1.93(1.24-3.0)], and HR [3.5(1.5-8.1)]. The median age of HD 37 (IQR 30-47) years was significantly lower than sibling donors 56 (IQR 49-62 years) p < 0.001. However, there was no effect on NRM, relapse or PFS. This data set suggests that a MSD donor remains the preferred choice in MDS over a haplo donor. Transplants with haploidentical donors result in satisfactory long-term outcome, justifying it's use when no better donor is available., (© 2022. The Author(s).)
- Published
- 2022
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20. Predicting the outcome for patients with myelofibrosis undergoing an allogeneic hemopoietic stem cell transplant.
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Sora F, Giammarco S, Raiola AM, Di Grazia C, Bregante S, Gualandi F, Varaldo R, Chiusolo P, Sica S, Laurenti L, Innocenti I, Autore F, Metafuni E, Galli E, Bacigalupo A, and Angelucci E
- Subjects
- Humans, Transplantation Conditioning, Transplantation, Homologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation adverse effects, Primary Myelofibrosis diagnosis, Primary Myelofibrosis etiology, Primary Myelofibrosis therapy
- Published
- 2022
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21. The day 100 score predicts moderate to severe cGVHD, transplant mortality, and survival after hematopoietic cell transplantation.
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Metafuni E, Cavattoni IM, Lamparelli T, Raiola AM, Ghiso A, Galaverna F, Gualandi F, Di Grazia C, Dominietto A, Varaldo R, Signori A, Chiusolo P, Sora' F, Giammarco S, Laurenti L, Sica S, Angelucci E, and Bacigalupo A
- Subjects
- Humans, Incidence, Transplantation Conditioning adverse effects, Transplantation, Homologous adverse effects, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
The aim of this study was to develop a predictive score for moderate-severe chronic graft-versus-host disease (cGVHD) on day +100 after allogeneic stem cell transplantation (HSCT). We studied 1292 patients allografted between 1990 and 2016, alive on day +100 after transplant, without cGVHD, and with full biochemistry laboratory values available. Patients were randomly assigned to a training and a validation cohort (ratio 1:1). In the training cohort, a multivariate analysis identified 4 independent predictors of moderate-severe cGVHD: gamma-glutamyl transferase ≥75 UI/l, creatinine ≥1 mg/dl, cholinesterase ≤4576 UI/l, and albumin ≤4 g/dl. A score of 1 was assigned to each variable, producing a low (0 to 1), intermediate (2 to 3), and high (4) score. The cumulative incidence of moderate-severe cGVHD was 12%, 20%, and 52% (P < .0001) in the training cohort, and 13%, 24%, and 33% (P = .002) in the validation cohort, respectively. The 5-year cumulative incidence of transplant-related mortality (TRM) was 5%, 14%, 27% (P < .0001) and 5%, 16%, 31% (P < .0001), respectively. The 5-year survival was 64%, 57%, 54% (P = .009) and 70%, 59%, 42% (P = .0008) in the 2 cohorts, respectively. In conclusion, Day100 score predicts cGVHD, TRM, and survival and, if validated in a separate group of patients, could be considered for trials of preemptive therapy., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2022
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22. Full donor chimerism after allogeneic hematopoietic stem cells transplant for myelofibrosis: The role of the conditioning regimen.
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Chiusolo P, Bregante S, Giammarco S, Lamparelli T, Casarino L, Dominietto A, Raiola AM, Metafuni E, Di Grazia C, Gualandi F, Sora F, Laurenti L, Sica S, Barosi G, Guolo F, Rossi M, Rossi E, Vannucchi A, Signori A, De Stefano V, Bacigalupo A, and Angelucci E
- Subjects
- Adult, Aged, Allografts, Busulfan administration & dosage, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Melphalan administration & dosage, Middle Aged, Splenectomy, Survival Rate, Thiotepa administration & dosage, Hematopoietic Stem Cell Transplantation, Primary Myelofibrosis mortality, Primary Myelofibrosis therapy, Transplantation Chimera, Transplantation Conditioning
- Abstract
The aim of this retrospective study was to assess the rate of full donor chimerism (F-DC) in patients with myelofibrosis, prepared for an allogeneic stem cell transplant, with one or two alkylating agents. We analyzed 120 patients with myelofibrosis, for whom chimerism data were available on day +30. There were two groups: 42 patients were conditioned with one alkylating agent (ONE-ALK), either thiotepa or busulfan or melphalan, in combination with fludarabine, whereas 78 patients were prepared with two alkylating agents, thiotepa busulfan and fludarabine (TBF). Patients receiving TBF were older (57 vs 52 years), were less frequently splenectomized pre-HSCT (31% vs 59%), had more frequently intermediate-2/high DIPSS scores (90% vs 74%), were grafted more frequently from alternative donors (83% vs 33%) and received more frequently ruxolitinib pre-HSCT (26% vs 7%). The proportion of patients with F-DC on day +30, in the TBF vs the ONE-ALK group, was respectively 87% vs 45% (P < .001). The 5-year cumulative incidence of relapse was 9% in the TBF group, vs 43% for the ONE-ALK group (P < .001). The 5-year actuarial disease-free survival was 63% for TBF and 38% for the ONE-ALK group (P = .004). In conclusion, early full donor chimerism is a prerequisite for long term control of disease in patients with myelofibrosis, undergoing an allogeneic HSCT. The combination of two alkylating agents in the conditioning regimen, provides a higher chance of achieving full donor chimerism on day+30, and thus a higher chance of long term disease free survival., (© 2020 Wiley Periodicals LLC.)
- Published
- 2021
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23. Enhancing the diagnosis of maxillary transverse discrepancy through 3-D technology and surface-to-surface superimposition. Description of the digital workflow with a documented case report.
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Lo Giudice A, Nucera R, Ronsivalle V, Di Grazia C, Rugeri M, and Quinzi V
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- Child, Female, Humans, Palatal Expansion Technique, Workflow, Malocclusion, Maxilla
- Abstract
Background: Maxillary transverse discrepancy is often diagnosed in childhood. The evaluation of morphological characteristics of the maxilla is crucial for appropriate treatment of this condition, however conventional diagnostic method is based on visual inspection and transversal linear parameters. In this paper, we described a user-friendly diagnostic digital workflow based on the surface-to-surface analysis. We also described a case report., Case Report: A 6-year-old female patient presenting mild transversal maxillary deficiency associated with functional posterior crossbite was treated by using maxillary removable appliance. In this respect, the appliance was designed in accordance to the morphological characteristics of the maxilla obtained by using the diagnostic digital work-flow and the maxillary surface-to-surface analysis., Conclusion: The present user-friendly diagnostic digital workflow based on surface-to-surface analysis helps clinicians to detect specific morphological characteristics of the maxilla, such as shape and area of asymmetry, in order to reach a comprehensive diagnosis and choose the correct biomechanics for treating the condition.
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- 2020
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24. Hepatitis E Virus Infection in an Italian Cohort of Hematopoietic Stem Cell Transplantation Recipients: Seroprevalence and Infection.
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Furfaro E, Nicolini L, Della Vecchia A, Di Grazia C, Raiola AM, Varaldo R, Ferrando F, Barisione G, Bruzzone B, Angelucci E, Viscoli C, and Mikulska M
- Subjects
- Aged, Humans, Italy epidemiology, Prospective Studies, RNA, Viral, Retrospective Studies, Seroepidemiologic Studies, Hematopoietic Stem Cell Transplantation adverse effects, Hepatitis E diagnosis, Hepatitis E epidemiology, Hepatitis E etiology, Hepatitis E virus genetics
- Abstract
Chronic hepatitis E virus (HEV) infection in hematopoietic stem cell transplantation (HSCT) recipients is an emerging threat. The aim of this study was to provide data on the HEV burden in an Italian cohort of HSCT recipients and analyze risk factors for HEV seropositivity. This retrospective study reports data from 596 HSCT recipients compiled between 2010 and 2019. It included patients who underwent transplantation between 2010 and 2015 for whom pretransplantation (n = 419) and post-transplantation (n = 161) serum samples were available and tested retrospectively, as well as patients in whom prospective HEV testing was performed during the standard care: pre-HSCT IgG screening in 144, pre-HSCT HEV-RNA screening in addition to IgG screening in 60, and HEV-RNA testing in case of clinical suspicion of HEV infection in 59 (26 of whom were also included in the IgG screening cohorts). The rate of pre-HSCT HEV-IgG positivity was 6.0% (34 of 563). Older age was an independent risk factor for seropositivity (P = .039). None of the 34 HEV-IgG-positive patients had detectable HEV-RNA. One case of transient HEV-RNA positivity pre-HSCT was identified through screening. Two patients were diagnosed with chronic HEV hepatitis, and 1 patient was successfully treated with ribavirin. The burden of HEV infection in HSCT recipients in Italy is limited, and pre-HSCT screening appears to be of no benefit. Timely diagnosis of HEV infection with HEV-RNA is mandatory in cases of clinical suspicion., (Copyright © 2020. Published by Elsevier Inc.)
- Published
- 2020
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25. A Modified Post-Transplant Cyclophosphamide Regimen, for Unmanipulated Haploidentical Marrow Transplantation, in Acute Myeloid Leukemia: A Multicenter Study.
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Chiusolo P, Bug G, Olivieri A, Brune M, Mordini N, Alessandrino PE, Dominietto A, Raiola AM, Di Grazia C, Gualandi F, Van Lint MT, Ferrara F, Finizio O, Angelucci E, and Bacigalupo A
- Subjects
- Adolescent, Adult, Aged, Cyclosporine therapeutic use, Drug Administration Schedule, Graft Survival, Graft vs Host Disease, Humans, Leukemia, Myeloid, Acute mortality, Middle Aged, Multivariate Analysis, Myeloablative Agonists administration & dosage, Predictive Value of Tests, Survival Analysis, Young Adult, Bone Marrow Transplantation methods, Cyclophosphamide therapeutic use, Leukemia, Myeloid, Acute therapy, Transplantation, Haploidentical methods
- Abstract
We report a modified post-transplant cyclophosphamide (PT-CY) regimen, for unmanipulated haploidentical marrow transplants, in 150 patients with acute myeloid leukemia (AML). All patients received a myeloablative regimen, cyclosporine A (CsA) on day 0, mycophenolate on day +1, and PT-CY 50 mg/kg on days +3 and +5. The median age was 51 (range, 17-74) years, 51 (34%) patients had active disease at transplant, and the median follow-up of surviving patients 903 (range, 150-1955) days. The cumulative incidence (CI) of engraftment, acute graft-versus-host disease (GVHD) grade II to IV, and moderate/severe chronic GVHD was 92%, 17%, and 15%, respectively. The 4-year CI of transplant-related mortality (TRM) and relapse was 20% and 24%, respectively. Four-year survival for remission patients was 72% (74% versus 67% for <60 or ≥60 years of age) and 26% for advanced patients (17% versus 41% for <60 or ≥60 years of age). In a multivariate analysis, active disease at transplant was the only negative predictor of survival, TRM and relapse. The original PT-CY regimen can be modified with CsA on day 0, still providing protection against GVHD, low toxicity, and encouraging low relapse incidence in AML patients, also over 60 years of age., (Copyright © 2018. Published by Elsevier Inc.)
- Published
- 2018
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26. High vs low dose cyclosporine-a, after allogeneic marrow transplantation in leukemia: Long term follow up of a randomized study.
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Bacigalupo A, Van Lint MT, Sica S, Laurenti L, Rosales MB, Dominietto A, di Grazia C, and Angelucci E
- Published
- 2018
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27. Impact of HLA Disparity in Haploidentical Bone Marrow Transplantation Followed by High-Dose Cyclophosphamide.
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Raiola AM, Risitano A, Sacchi N, Giannoni L, Signori A, Aquino S, Bregante S, Di Grazia C, Dominietto A, Geroldi S, Ghiso A, Gualandi F, Lamparelli T, Tedone E, Van Lint MT, Varaldo R, Ibatici A, Marani C, Marotta S, Guolo F, Avenoso D, Garbarino L, Pane F, Bacigalupo A, and Angelucci E
- Subjects
- Bone Marrow Transplantation mortality, Graft Rejection immunology, Graft vs Host Disease prevention & control, Humans, Survival Analysis, Transplantation, Haploidentical mortality, Bone Marrow Transplantation adverse effects, Cyclophosphamide therapeutic use, HLA Antigens immunology, Histocompatibility immunology, Transplantation, Haploidentical adverse effects
- Abstract
We studied the impact of HLA mismatching on the outcome of 318 consecutive patients who received an unmanipulated haploidentical bone marrow transplant, followed by post-transplant cyclophosphamide (PTCy). The number of HLA-mismatched antigens was tested for its impact on overall survival (OS) and nonrelapse mortality (NRM), whereas HLA mismatches in the graft-versus-host (GVH) direction were tested for prediction of graft-versus-host disease (GVHD and relapse. Finally, we studied whether graft rejection correlated with the number of HLA mismatched antigens in host-versus-graft (HVG) direction. Two hundred thirty-one donor-recipient pairs (72%) had 4/8 mismatches at the -A, -B, -C, -DRB1 HLA loci. HLA mismatches did not predict the 2-year OS (hazard ratio, .83; P = .58) and NRM (subhazard ratio, 1.08; P = .93). The cumulative incidence of acute GVHD (P = .13), 1-year chronic GVHD (P = .84), and relapse rate (P = .26) did not correlate with univectorial GVH mismatches. Similarly, no correlation was observed between the amount of HLA mismatch in the HVG direction and graft rejection. In multivariate analysis advanced disease at transplant was the strongest predictor of survival, NRM, relapse, and graft rejection. In conclusion, the degree of HLA mismatching should not be used as a criterion to select family haploidentical donors when using bone marrow as stem cell source and PTCy for GVHD prophylaxis., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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28. Combining flow cytometry and WT1 assessment improves the prognostic value of pre-transplant minimal residual disease in acute myeloid leukemia.
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Guolo F, Minetto P, Clavio M, Miglino M, Galaverna F, Raiola AM, Di Grazia C, Colombo N, Pozzi S, Ibatici A, Bagnasco S, Guardo D, Kunkl A, Ballerini F, Ghiggi C, Lemoli RM, Gobbi M, and Bacigalupo A
- Subjects
- Follow-Up Studies, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute pathology, Leukemia, Myeloid, Acute therapy, Prognosis, Recurrence, Retrospective Studies, Survival Analysis, Flow Cytometry methods, Leukemia, Myeloid, Acute diagnosis, Neoplasm, Residual diagnosis, WT1 Proteins analysis
- Published
- 2017
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29. Haploidentical bone marrow transplantation in patients with advanced myelodysplastic syndrome.
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Varaldo R, Raiola AM, Di Grazia C, Aquino S, Beltrami G, Bregante S, Cruciani F, Dominietto A, Ghiso A, Giannoni L, Gualandi F, Ibatici A, Lamparelli T, Marani C, Van Lint MT, Santini V, Bacigalupo A, and Angelucci E
- Subjects
- Adult, Aged, Allografts, Disease-Free Survival, Female, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Myelodysplastic Syndromes mortality, Time-to-Treatment, Transplantation Conditioning, Treatment Outcome, Bone Marrow Transplantation, Hematopoietic Stem Cell Transplantation, Histocompatibility, Living Donors, Myelodysplastic Syndromes therapy
- Published
- 2017
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30. High feasibility and antileukemic efficacy of fludarabine, cytarabine, and idarubicin (FLAI) induction followed by risk-oriented consolidation: A critical review of a 10-year, single-center experience in younger, non M3 AML patients.
- Author
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Guolo F, Minetto P, Clavio M, Miglino M, Di Grazia C, Ballerini F, Pastori G, Guardo D, Colombo N, Kunkl A, Fugazza G, Rebesco B, Sessarego M, Lemoli RM, Bacigalupo A, and Gobbi M
- Subjects
- Adolescent, Adult, Aged, Aminoglycosides therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Child, Cytarabine administration & dosage, Female, Gemtuzumab, Humans, Idarubicin administration & dosage, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Retrospective Studies, Survival Analysis, Survival Rate, Treatment Outcome, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Vidarabine toxicity, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Consolidation Chemotherapy methods, Induction Chemotherapy methods, Leukemia, Myeloid, Acute drug therapy
- Abstract
About 105 consecutive acute myeloid leukemia (AML) patients treated with the same induction-consolidation program between 2004 and 2013 were retrospectively analyzed. Median age was 47 years. The first induction course included fludarabine (Flu) and high-dose cytarabine (Ara-C) plus idarubicin (Ida), with or without gemtuzumab-ozogamicin (GO) 3 mg/m(2) (FLAI-5). Patients achieving complete remission (CR) received a second course without fludarabine but with higher dose of idarubicin. Patients not achieving CR received an intensified second course. Patients not scheduled for early allogeneic bone marrow transplantation (HSCT) where planned to receive at least two courses of consolidation therapy with Ara-C. Our double induction strategy significantly differs from described fludarabine-containing regimens, as patients achieving CR receive a second course without fludarabine, to avoid excess toxicity, and Ara-C consolidation is administrated at the reduced cumulative dose of 8 g/m(2) per cycle. Toxicity is a major concern in fludarabine containing induction, including the recent Medical Research Council AML15 fludarabine, cytarabine, idaraubicin and G-CSF (FLAG-Ida) arm, and, despite higher anti-leukemic efficacy, only a minority of patients is able to complete the full planned program. In this article, we show that our therapeutic program is generally well tolerated, as most patients were able to receive subsequent therapy at full dose and in a timely manner, with a 30-day mortality of 4.8%. The omission of fludarabine in the second course did not reduce efficacy, as a CR rate of 83% was achieved and 3-year disease-free survival and overall survival (OS) were 49.6% and 50.9%, respectively. Our experience shows that FLAI-5/Ara-C + Ida double induction followed by risk-oriented consolidation therapy can result in good overall outcome with acceptable toxicity. Am. J. Hematol. 91:755-762, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2016
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31. Wilms Tumor 1 Expression and Pre-emptive Immunotherapy in Patients with Acute Myeloid Leukemia Undergoing an Allogeneic Hemopoietic Stem Cell Transplantation.
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Di Grazia C, Pozzi S, Geroldi S, Grasso R, Miglino M, Colombo N, Tedone E, Luchetti S, Lamparelli T, Gualandi F, Ibatici A, Bregante S, Van Lint MT, Raiola AM, Dominietto A, Varaldo R, Galaverna F, Ghiso A, Sica S, and Bacigalupo A
- Subjects
- Adolescent, Adult, Aged, Bone Marrow Cells metabolism, Female, Humans, Immunotherapy, Adoptive, Leukemia, Myeloid, Acute mortality, Lymphocyte Transfusion, Male, Middle Aged, Transplantation, Homologous, Young Adult, Hematopoietic Stem Cell Transplantation methods, Immunotherapy methods, Leukemia, Myeloid, Acute therapy, Premedication methods, WT1 Proteins analysis
- Abstract
Minimal residual disease (MRD) was monitored by Wilms tumor 1 (WT1) expression in 207 patients with acute myeloid leukemia (AML) after an allogeneic hemopoietic stem cell transplantation (HSCT) as a trigger to initiate pre-emptive immunotherapy (IT) with cyclosporin discontinuation and/or donor lymphocyte infusion. The trigger for IT was WT1 ≥ 180 copies/10(4) Abelson cells in marrow cells in the first group of 122 patients (WT1-180) and ≥ 100 copies in a subsequent group of 85 patients (WT1-100). Forty patients received IT. The cumulative incidence (CI) of relapse was 76% in WT1-180 (n = 17) versus 29% in WT1-100 patients (n = 23) receiving IT (P = .006); the leukemia-free survival from MRD positivity was 23% versus 74%, respectively (P = .003). We then looked at the entire AML patient population (n = 207). WT1-180 and WT1-100 patients were comparable for disease phase and age. The overall 4-year CI of transplantation-related mortality was 13% in both groups; the CI of leukemia relapse was 38% in the WT1-180 and 28% in the WT1-100 patients (P = .05) and leukemia-free survival was 56% versus 48%, respectively (P = .07). In conclusion, we suggests that WT1-based pre-emptive immunotherapy is feasible in patients with undergoing an allogeneic HSCT. The protective effect on relapse is greater when IT is triggered at lower levels of WT1., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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32. Improved Outcome of Alternative Donor Transplantations in Patients with Myelofibrosis: From Unrelated to Haploidentical Family Donors.
- Author
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Bregante S, Dominietto A, Ghiso A, Raiola AM, Gualandi F, Varaldo R, Di Grazia C, Lamparelli T, Luchetti S, Geroldi S, Casarino L, Pozzi S, Tedone E, Van Lint MT, Galaverna F, Barosi G, and Bacigalupo A
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Primary Myelofibrosis mortality, Retrospective Studies, Survival Analysis, Treatment Outcome, Unrelated Donors, Young Adult, Hematopoietic Stem Cell Transplantation methods, Primary Myelofibrosis therapy, Transplantation Conditioning methods, Transplantation, Homologous methods
- Abstract
This is a retrospective analysis of 95 patients with myelofibrosis who were allografted between 2001 and 2014. The aims of the study were to assess whether the outcome of alternative donor grafts has improved with time and how this compares with the outcome of identical sibling grafts. Patients were studied in 2 time intervals: 2000 to 2010 (n = 58) and 2011 to 2014 (n = 37). The Dynamic International Prognostic Scoring System score was comparable in the 2 time periods, but differences in the most recent group included older age (58 versus 53 years, P = .004), more family haploidentical donors (54% versus 5%, P < .0001), and the introduction of the thiotepa-fludarabine-busulfan conditioning regimen (70% of patients versus 2%, P < .0001). Acute and chronic graft-versus-host disease were comparable in the 2 time periods. The 3-year transplantation-related mortality (TRM) in the 2011 to 2014 period versus the 2000 to 2010 period is 16% versus 32% (P = .10), the relapse rate 16% versus 40% (P = .06), and actuarial survival 70% versus 39% (P = .08). Improved survival was most pronounced in alternative donor grafts (69% versus 21%, P = .02), compared with matched sibling grafts (72% versus 45%, P = .40). In conclusion, the outcome of allografts in patients with myelofibrosis has improved in recent years because of a reduction of both TRM and relapse. Improvement is most significant in alternative donor transplantations, with modifications in donor type and conditioning regimen., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
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33. Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts.
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Raiola AM, Dominietto A, di Grazia C, Lamparelli T, Gualandi F, Ibatici A, Bregante S, Van Lint MT, Varaldo R, Ghiso A, Gobbi M, Carella AM, Signori A, Galaverna F, and Bacigalupo A
- Subjects
- Adolescent, Adult, Aged, Female, Gene Expression, HLA Antigens genetics, HLA Antigens immunology, Haplotypes, Hematologic Neoplasms genetics, Hematologic Neoplasms immunology, Hematologic Neoplasms mortality, Histocompatibility Testing, Humans, Immunosuppressive Agents therapeutic use, Male, Middle Aged, Myeloablative Agonists therapeutic use, Prospective Studies, Recurrence, Siblings, Survival Analysis, Transplantation, Homologous, Unrelated Donors, Cord Blood Stem Cell Transplantation, Graft vs Host Disease prevention & control, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation, Transplantation Conditioning methods
- Abstract
We studied 459 consecutive patients with hematologic malignancies, median age 44 years (range, 15 to 71 years), who underwent transplantation with grafts from identical sibling donors (SIB; n = 176), matched unrelated donors (MUD; n = 43), mismatched unrelated donors (mmUD; n = 43), unrelated cord blood (UCB; n = 105) or HLA-haploidentical family donors (HAPLO; n = 92). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate in the SIB recipients; antithymocyte globulin for the MUD, mmUD, and UCB recipients; and post-transplantation cyclophosphamide, cyclosporine, and mycophenolate in the HAPLO recipients. Conditioning regimens were mostly myeloablative (69%). Advanced disease phase was more frequent, but not significantly so, in the HAPLO and mmUD groups (P = .08). Acute GVHD grade II-IV was significantly less frequent in the HAPLO, UCB, and MUD groups (14% to 21%) compared with the SIB (31%) and mmUD (42%) groups (P < .001), and there was a trend toward less moderate-severe chronic GVHD in the HAPLO and UCB groups (P = .053). The proportion of patients off cyclosporine at 1 year ranged from 55% for the SIB group to 81% for the HAPLO group (P < .001). Transplantation-related mortality at 2 years was lower in the HAPLO and SIB groups (18% to 24%) compared with the MUD, mmUD, and UCB groups (33% to 35%; P = .10). Relapse rate was comparable in the 5 groups (P = .80). The 4-year actuarial survival was 45% in the SIB group, 43% in the MUD group, 40% in the mmUD group, 34% in the UCB group, and 52% in the HAPLO group (P = .10). In multivariate analysis, advanced disease was a negative predictor of survival (hazard ratio [HR], 2.4; P < .0001), together with a diagnosis of acute leukemia (HR, 1.8; P = .0001); HAPLO grafts were comparable to SIB (P = .80), whereas UCB had inferior survival (P = .03). In conclusion, unmanipulated haploidentical family donor transplants are an additional option for patients lacking a matched sibling donor., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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34. CD34 selected cells for the treatment of poor graft function after allogeneic stem cell transplantation.
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Stasia A, Ghiso A, Galaverna F, Raiola AM, Gualandi F, Luchetti S, Pozzi S, Varaldo R, Lamparelli T, Bregante S, Van Lint MT, di Grazia C, and Bacigalupo A
- Subjects
- Adolescent, Adult, Antigens, CD34, Female, Humans, Male, Middle Aged, Treatment Outcome, Young Adult, Graft Survival physiology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects, Transplantation Conditioning adverse effects
- Abstract
Poor graft function (PGF) is characterized by pancytopenia and a hypoplastic marrow, with complete donor chimerism, usually without severe graft-versus-host disease (GVHD). We report 41 patients with PGF, treated with granulocyte colony-stimulating factor-mobilized CD34 selected cells, at a median interval from transplant of 140 days, without conditioning and without GVHD prophylaxis. Donors were HLA matched siblings (n = 12), unrelated donors (n = 18), or mismatched family members (n = 11). The median number of infused CD34(+) cells was 3.4 × 10(6)/kg. The rate of trilineage recovery was 75%: 83% for HLA matched siblings and 72% for unrelated and mismatched family members (P = .3). The cumulative incidence of acute grade II GVHD was 15%, and no patient developed de novo chronic GVHD. The actuarial 3-year survival is 63%: 76% and 25% for patients with or without trilineage recovery. These data confirm the role of CD34(+) selected cells from the same donor in the treatment of PGF and warrant the request for a second donation also when the donor is unrelated., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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35. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning.
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Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, Bregante S, Van Lint MT, Geroldi S, Luchetti S, Ballerini F, Miglino M, Varaldo R, and Bacigalupo A
- Subjects
- Acute Disease, Adolescent, Adult, Aged, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Busulfan administration & dosage, Busulfan adverse effects, Chronic Disease, Cyclophosphamide adverse effects, Disease-Free Survival, Female, Follow-Up Studies, Graft vs Host Disease etiology, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Humans, Immunosuppressive Agents adverse effects, Male, Middle Aged, Myeloablative Agonists administration & dosage, Myeloablative Agonists adverse effects, Retrospective Studies, Survival Rate, Thiotepa administration & dosage, Thiotepa adverse effects, Transplantation, Homologous, Vidarabine administration & dosage, Vidarabine adverse effects, Vidarabine analogs & derivatives, Whole-Body Irradiation, Bone Marrow Transplantation, Cyclophosphamide administration & dosage, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Immunosuppressive Agents administration & dosage, Transplantation Conditioning
- Abstract
Fifty patients with high-risk hematologic malignancies, underwent an unmanipulated haploidentical bone marrow transplantation (BMT), followed by posttransplantation high-dose cyclophosphamide (PT-CY): the myeloablative (MA) conditioning consisted of thiotepa, busulfan, fludarabine (n = 35), or total body irradiation (TBI), fludarabine (n = 15). The median age was 42 years (range, 18-66 years); 23 patients were in remission, 27 had active disease, and 10 patients were receiving a second allograft. Graft-versus-host disease (GVHD) prophylaxis consisted in PT-CY on day +3 and +5, cyclosporine (from day 0), and mycophenolate (from day +1). Three patients died before engraftment, and 2 patients had autologous recovery: 45 patients (90%) had full-donor chimerism on day +30. The median day for neutrophil engraftment was day +18 (range, 13-30 days). The cumulative incidence of grade II-III acute GVHD (aGVHD) was 12%, and of moderate chronic GVHD (cGVHD) 10%. With a median follow-up for surviving patients of 333 days (range, 149-623 days), the cumulative incidence of transplantation-related mortality (TRM) was 18%, and the rate of relapse was 26%. The actuarial 22-month disease-free survival (DFS) rate was 68% for patients in remission and 37% for patients with active disease (P < .001). Causes of death were pneumonia (n = 3), hemorrhage (n = 3), sepsis (n = 3), and relapse (n = 7). In conclusion, an MA conditioning regimen followed by haploidentical BMT with PT-CY results in a low risk of aGVHD and cGVHD and encouraging rates of TRM and DFS., (Copyright © 2013 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2013
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36. Rituximab treatment for Epstein-Barr virus DNAemia after alternative-donor hematopoietic stem cell transplantation.
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Coppoletta S, Tedone E, Galano B, Soracco M, Raiola AM, Lamparelli T, Gualandi F, Bregante S, Ibatici A, di Grazia C, Dominietto A, Varaldo R, Bruno B, Frassoni F, Van Lint MT, and Bacigalupo A
- Subjects
- Antilymphocyte Serum administration & dosage, Blood Donors, DNA, Viral blood, Drug Dosage Calculations, Epstein-Barr Virus Infections blood, Epstein-Barr Virus Infections etiology, Epstein-Barr Virus Infections immunology, Epstein-Barr Virus Infections mortality, Female, Humans, Male, Middle Aged, Retrospective Studies, Rituximab, Survival Analysis, Transplantation, Transplantation, Homologous, Viremia blood, Viremia immunology, Viremia virology, Virus Activation drug effects, Antibodies, Monoclonal, Murine-Derived administration & dosage, Antilymphocyte Serum immunology, Epstein-Barr Virus Infections drug therapy, Epstein-Barr Virus Infections virology, Hematopoietic Stem Cell Transplantation adverse effects, Herpesvirus 4, Human, Transplantation Conditioning, Viremia drug therapy
- Abstract
We report 55 patients undergoing an alternative-donor hematopoietic stem cell transplantation (HSCT) who developed Epstein-Barr virus (EBV) DNAemia, with >1000 EBV copies/10(5) peripheral blood mononuclear cells (PBMCs), and were treated with rituximab (375 mg/m(2)). The median patient age was 47 years (range, 20-65 years), and graft sources were mismatched family members (n = 4), unrelated donors (n = 46), and unrelated cord blood (n = 5). The conditioning regimen included antithymocyte globulin (ATG) in all patients. The median time to development of EBV DNAemia was day 27 post-HSCT (range, day 5 to day 242), with a median of 60 EBV copies/10(5) PBMCs (range, 1-5770 copies/10(5) PBMCs). The number of EBV copies was reduced to <1000/10(5) PBMCs on day +7 after initiation of rituximab therapy in 51% of the patients, on day +14 in 73% of the patients, and on +21 in 92% of the patients. Overall, 50 of 55 patients (91%) cleared EBV after one dose (n = 25) or more than one dose (n = 25) of rituximab. Factors predicting transplantation-related mortality (TRM) in multivariate analysis were a reduction to <1000 EBV copies/10(5) PBMCs by day +7 of treatment (relative risk [RR], 0.2; P = .01) and disease phase in remission (RR, 0.3; P = .05). TRM was 23% in the 40 patients with none or one of the negative predictors and 60% in the 15 patients with both negative predictors (P = .001). Of these latter 15 patients, 3 developed clinical posttransplantation lymphoproliferative disorder (PTLD). All 3 of these patients had a high EBV load on day +7 of rituximab therapy. This study confirms the effectiveness of rituximab in controlling EBV DNAemia in patients undergoing allogeneic HSCT. Patients with increasing EBV copies despite rituximab therapy are at high risk for EBV PTLD and may be considered for alternative therapies., (Published by Elsevier Inc.)
- Published
- 2011
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37. Blood stream infections in allogeneic hematopoietic stem cell transplant recipients: reemergence of Gram-negative rods and increasing antibiotic resistance.
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Mikulska M, Del Bono V, Raiola AM, Bruno B, Gualandi F, Occhini D, di Grazia C, Frassoni F, Bacigalupo A, and Viscoli C
- Subjects
- Adolescent, Adult, Antibiotic Prophylaxis, Bacteremia microbiology, Female, Fluoroquinolones therapeutic use, Fungemia, Gram-Positive Bacteria isolation & purification, Hematopoietic Stem Cell Transplantation mortality, Hematopoietic Stem Cell Transplantation statistics & numerical data, Humans, Male, Middle Aged, Retrospective Studies, Transplantation, Homologous, Young Adult, Bacteremia etiology, Drug Resistance, Microbial, Gram-Negative Bacteria isolation & purification, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Blood stream infections (BSI) are a well-known cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) patients. The aim of this study was to analyze etiology and microbial resistance of BSI in patients undergoing allogeneic HSCT in a single center over a 4-year period (2004-2007). There were 168 episodes of BSI in 132 patients (median 10 days after HSCT) and 182 pathogens were isolated. Gram-positive bacteria (GPB) accounted for 57% of 182 isolates. Gram-negative rods (GNR) for 37% and fungi for 6%. All patients received routine fluoroquinolone prophylaxis. There was a significant decrease in GPB/GNR ratio over time, from 2.4 in 2004 to 1 in 2007 (P = .043). Among GPB, staphylococci decreased from 37 of 68 (64%) in 2004-2005 to 8 of 35 (23%) in 2006-2007 (P < .002). The Enterococcus faecalis/E. faecium ratio decreased from 4.5 in 2004 to 0.33 in 2007 (P = .006), whereas the total number of enterococcal strains per year did not change. The incidence of Escherichia coli among GNR increased from 3 of 15 (20%) in 2004 to 13 of 21 (62%) in 2007 (P = .003). Fluoroquinolone-resistance was common, both among GPB and GNR (81% and 74%, respectively). Mortality rate at 7 days after BSI was 11% (19 of 168), reaching 39% for Pseudomonas aeruginosa BSI (7 of 18). BSI remains a frequent and potentially life-threatening complication of allogeneic HSCT, the causative organism influencing 7- and 30-day mortality rate. BSI etiology may change rapidly, requiring implementation of new empirical-therapy schemes.
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- 2009
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38. Boost of CD34+-selected peripheral blood cells without further conditioning in patients with poor graft function following allogeneic stem cell transplantation.
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Larocca A, Piaggio G, Podestà M, Pitto A, Bruno B, Di Grazia C, Gualandi F, Occhini D, Raiola AM, Dominietto A, Bregante S, Lamparelli T, Tedone E, Oneto R, Frassoni F, Van Lint MT, Pogliani E, and Bacigalupo A
- Subjects
- Adolescent, Adult, Female, Graft vs Host Disease mortality, Humans, Male, Middle Aged, Peripheral Blood Stem Cell Transplantation adverse effects, Peripheral Blood Stem Cell Transplantation mortality, Transplantation, Homologous, Treatment Failure, Antigens, CD34, Graft Survival, Peripheral Blood Stem Cell Transplantation methods
- Abstract
Background and Objectives: A proportion of patients develop poor graft function (PGF) following an allogeneic hemopoietic stem cell transplant (HSCT). It is uncertain whether a boost of donor marrow or blood cells is beneficial in terms of trilineage recovery and non-relapse-related mortality (NRM)., Design and Methods: The aim of this study was to compare outcomes in patients with PGF and full donor chimerism following an allogeneic HSCT who did or did not receive a boost of donor stem cells. The study included patients with primary PGF--i.e. those failing to achieve sustained graft function- and secondary PGF--i.e. those developing PGF after complete hematologic recovery. We studied 54 patients with PGF: 20 patients received no further donor cell infusion (group A), 14 received a boost of unmanipulated marrow or blood cells from the original donor, without further conditioning (group B), and 20 received donor cells after CD34 selection without conditioning (group C). The three groups were comparable for disease phase, patients' age, donor type, primary or secondary PGF, full donor chimerism and duration of PGF., Results: Trilineage recovery was seen in 40%, 36% and 75% of the patients in, respectively, groups A, B and C (p=0.02). In multivariate Cox analysis trilineage recovery was more frequent in patients with secondary PGF (RR of complete recovery 2.82, p=0.01) and in patients receiving CD34+-selected cells (RR of complete recovery 3.0; p=0.007). There was no effect of donor type on hematologic recovery. The rate of NRM was 55%, 64%, 20% in groups A, B and C, respectively (p=0.06) and was highly correlated with trilineage recovery (RR 0.36, p<0.0001). PGF was the primary cause of death in 30%, 21% and 10% of the patients in the three groups, graft-versus-host disease (GVHD) in 5%, 36%, and 10%., Interpretations and Conclusions: In patients with poor graft function (a) a boost of CD34+-selected peripheral blood donor cells is associated with a high chance of trilineage recovery and a low risk of acute GVHD; (b) a boost of unmanipulated donor cells does not seem to offer a survival advantage over no infusion of cells; and (c) NRM is lower when using peripheral blood cells for the boost. These data may be useful when discussing second stem cell donations for patients with poor graft function.
- Published
- 2006
39. Reducing transplant-related mortality after allogeneic hematopoietic stem cell transplantation.
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Bacigalupo A, Sormani MP, Lamparelli T, Gualandi F, Occhini D, Bregante S, Raiola AM, di Grazia C, Dominietto A, Tedone E, Piaggio G, Podesta M, Bruno B, Oneto R, Lombardi A, Frassoni F, Rolla D, Rollandi G, Viscoli C, Ferro C, Garbarino L, and Van Lint MT
- Subjects
- Actuarial Analysis, Adult, Anti-Infective Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation statistics & numerical data, Cause of Death, Combined Modality Therapy, Female, Graft vs Host Disease etiology, Graft vs Host Disease mortality, Graft vs Host Disease prevention & control, Hematologic Neoplasms drug therapy, Hematologic Neoplasms mortality, Hematopoietic Stem Cell Transplantation mortality, Hematopoietic Stem Cell Transplantation statistics & numerical data, Humans, Immunosuppressive Agents adverse effects, Immunosuppressive Agents therapeutic use, Infection Control, Infections etiology, Infections mortality, Leukemia drug therapy, Leukemia mortality, Leukemia surgery, Lung Diseases, Interstitial etiology, Lung Diseases, Interstitial mortality, Male, Middle Aged, Multiple Organ Failure, Neutropenia chemically induced, Neutropenia complications, Peripheral Blood Stem Cell Transplantation adverse effects, Peripheral Blood Stem Cell Transplantation methods, Peripheral Blood Stem Cell Transplantation mortality, Peripheral Blood Stem Cell Transplantation statistics & numerical data, Premedication, Remission Induction, Retrospective Studies, Salvage Therapy, Survival Analysis, Transplantation Conditioning methods, Transplantation Conditioning mortality, Transplantation, Homologous methods, Transplantation, Homologous statistics & numerical data, Treatment Outcome, Bone Marrow Transplantation mortality, Hematologic Neoplasms surgery, Transplantation, Homologous mortality
- Abstract
Background and Objectives: Transplant-related mortality (TRM) following allogeneic hematopoietic stem cell transplantation (HSCT) has been reported to be related to disease stage, duratiion of disease and type of donor. Furthermore, the outcome of transplants performed in the 1990s appears to be better than that of transplants done in the previous decade. The aims of this study were to determine whether these relationships still hold and whether the outcome of transplants is continuing to improve., Design and Methods: We analyzed 1180 consecutive patients with leukemia (n=979) or other hematologic malignancies (n=201) undergoing HSCT in 4 time periods: before 1990, 1991-1995, 1996-2000, and 2001-2002. Changes during these eras include increasing patient age, more unrelated transplants, more patients with advanced disease, different graft-versus-host disease (GvHD) prophylaxis, and different management of infections., Results: The actuarial 2-year transplant-related mortality (TRM) differed significantly between the transplant eras (p<0.001) with a significant interaction with disease phase (p=0.018). In patients in first remission (n=585) TRM was 34%, 25%, 21% and 6% in the four transplant eras. The reduction in TRM was less evident in patients in second remission (n=284) (37%, 35%, 30%, 25%) and absent in relapsed patients (n=311) (TRM=45%, 41%, 29%, 51%). This is a consequence of reductions in GvHD, infections and multiorgan failure among patients in remission but not among those who relapse. The actuarial 2-year survival has improved significantly in patients in first remission (54%, 66%, 72%, 78%) but not in those in second remission (38%, 46%, 52%,45%), or relapsed patients (31%, 25%, 36%, 21%)., Interpretation and Conclusions: In conclusion, TRM has been significantly reduced in first remission patients, suggesting an allograft should be considered in this phase, when appropriate, without delay. There has been no improvement in survival for patients beyond first remission, due to persisting high risk of infections and organ toxicity, a possible consequence of prolonged pre-transplant chemotherapy and neutropenia.
- Published
- 2004
40. Transplant-related mortality and long-term graft function are significantly influenced by cell dose in patients undergoing allogeneic marrow transplantation.
- Author
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Dominietto A, Lamparelli T, Raiola AM, Van Lint MT, Gualandi F, Berisso G, Bregante S, Di Grazia C, Soracco M, Pitto A, Frassoni F, and Bacigalupo A
- Subjects
- Adolescent, Adult, Aged, Bone Marrow Transplantation adverse effects, Cause of Death, Cell Count, Child, Child, Preschool, Female, Hemoglobins metabolism, Humans, Infant, Leukocyte Count, Male, Middle Aged, Multivariate Analysis, Platelet Count, Recurrence, Survival Analysis, Transplantation, Homologous adverse effects, Transplantation, Homologous methods, Transplantation, Homologous mortality, Bone Marrow Transplantation methods, Bone Marrow Transplantation mortality, Graft Survival physiology
- Abstract
We have studied the impact of cell dose on short- and long-term graft function and outcome in 905 patients undergoing an unmanipulated allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling (n = 735), a one-antigen mismatched related donor (n = 35), or a matched unrelated donor (n = 135). Median number of nucleated cells infused was 3.4 x 10(8)/kg (25th percentile 2.4 x 10(8)/kg, 75th percentile 5 x 10(8)/kg). Patients were stratified according to cells infused in 3 groups: < or = 2.4 x 10(8)/kg (n = 247; low dose); >2.4 x 10(8)/kg and < or = 5 x 10(8)/kg (n = 452; intermediate dose); and >5 x 10(8)/kg (n = 206; high dose). Patients receiving high cell dose had significantly higher platelet counts on days +20, +50, +100, +180, and +365 after BMT (P <.01) and higher white blood cell counts on days +50, +100, and +180 after BMT (P <.01) as compared with other patients. The actuarial 5-year transplant-related mortality (TRM) was 41% versus 36% versus 28% (P =.01); overall survival was 45% versus 51% versus 56% (P =.0008); and disease-free survival was 41% versus 42% versus 48%, respectively, (P =.04) in patients receiving low, intermediate, or high cell dose. The cell dose effect was more pronounced in patients older than 30 years of age, with advanced disease, with chronic myeloid leukemia, and with alternative donors. In multivariate Cox analysis on TRM, cell dose was a significant predictor (P =.002; relative risk 0.6) together with donor type (P =.0001), year of transplantation (P =.0001), conditioning regimen (P =.02), and recipient age (P =.02). In conclusion, transplantation of high marrow cell dose is associated with reduced transplant mortality and improved survival and results in improved graft function both short and long term.
- Published
- 2002
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41. Treatment of acute graft versus host disease with low dose-alternate day anti-thymocyte globulin.
- Author
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Graziani F, Van Lint MT, Dominietto A, Raiola AM, Di Grazia C, Lamparelli T, Gualandi F, Bregante S, Fiorone M, Bruno B, and Bacigalupo A
- Subjects
- Adult, Bone Marrow Transplantation immunology, Bone Marrow Transplantation mortality, Graft vs Host Disease mortality, Humans, Infections, Middle Aged, Survival Rate, Time Factors, Antilymphocyte Serum administration & dosage, Antilymphocyte Serum therapeutic use, Graft vs Host Disease drug therapy
- Abstract
Background and Objectives: The efficacy of antithymocyte globulin (ATG) in the treatment of graft-versus-host disease (GvHD) is controversial. In the present study we report on the use of low dose ATG (thymoglobuline, Sangstat) and steroids in 28 patients with moderate to severe acute GvHD., Design and Methods: Fifteen patients received ATG as first-line treatment within 14 days of the diagnosis of GvHD (median 8 days, range 4-13). Twelve patients received ATG as second-line therapy, more than 14 days after diagnosis (median 32 days, range 14 to 98). The proportion of patients with severe (grade III-IV) GvHD at the time of ATG therapy was 4/15 in the former group and 7/13 in the latter (p=0.1)., Results: On day 30 after ATG the overall proportion of responders was 80% in the group administered ATG early and 38% in those given it later (p=0.03). The overall actuarial 3-year transplant-related mortality was 40% vs 74% for the early vs late ATG groups (p=0.03); the actuarial 3-year survival was, respectively, 49% vs 23% (p=0.04). For patients with GvHD grade III-IV the actuarial 1-year TRM was 47% for those given ATG early, 87% for the late ATG group and 82% for a concurrent control group of 26 patients not treated with ATG., Interpretation and Conclusions: In conclusion, ATG may be considered for early treatment of acute GvHD, within a few days from the onset of the disease. A prospective trial has been started to test whether, in this setting, low dose ATG with steroids is superior to steroids alone.
- Published
- 2002
42. High prevalence of hepatitis G virus infection in Hodgkin's disease and B-cell lymphoproliferative disorders: absence of correlation with hepatitis C virus infection.
- Author
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De Renzo A, Persico E, de Marino F, di Giacomo Russo G, Notaro R, di Grazia C, Picardi M, Santoro L, Torella R, Rotoli B, and Persico M
- Subjects
- Adolescent, Adult, Aged, B-Lymphocytes pathology, Comorbidity, Female, Flaviviridae Infections complications, Flaviviridae Infections epidemiology, Hepacivirus, Hepatitis C complications, Hepatitis C diagnosis, Hepatitis C epidemiology, Hepatitis, Viral, Human diagnosis, Hepatitis, Viral, Human epidemiology, Hodgkin Disease epidemiology, Hodgkin Disease etiology, Humans, Italy epidemiology, Lymphoproliferative Disorders epidemiology, Lymphoproliferative Disorders etiology, Male, Middle Aged, Prevalence, GB virus C, Hepatitis, Viral, Human complications, Hodgkin Disease virology, Lymphoproliferative Disorders virology
- Abstract
Background and Objectives: During the last decade an epidemiological association between hepatitis C virus (HCV) and B-cell lymphoproliferative disorders (B-LPD) has been reported; the same association has not been observed for Hodgkin's disease (HD). Hepatitis G virus (HGV) shares genetic and biological features with HCV, thus it might also be involved in lymphomagenesis., Design and Methods: The aim of this study was to compare the prevalence of HCV and HGV infection in patients at diagnosis of B-LPD or HD., Results: We tested 227 consecutive untransfused patients (127 with B-LPD and 100 with HD) and 110 healthy controls. The prevalence of HCV infection was significantly higher in B-LPD patients than in controls (17.3% vs. 1.8%, p<0.002 ), whereas it was the same in HD patients as in controls. In contrast, the prevalence of HGV was significantly higher in patients, both those with B-LPD (7.8% vs. 0.9%, p<0.03) and those with HD (13% vs. 0.9%, p<0.002), than in controls. Among the various B-LPD tested, HGV infection was more frequent in B-NHL (11.5%)., Interpretation and Conclusions: Our data support the hypothesis that HGV infection may play a role in lymphomagenesis and that this role is different and separate from that of HCV.
- Published
- 2002
43. Increased risk of leukemia relapse with high dose cyclosporine after allogeneic marrow transplantation for acute leukemia: 10 year follow-up of a randomized study.
- Author
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Bicigalupo A, Lamparelli T, Gualandi F, Bregante S, Raiola A, di Grazia C, Dominietto A, Romagnani C, Occhini D, Frassoni F, and van Lint MT
- Subjects
- Adolescent, Adult, Age Factors, Child, Child, Preschool, Cohort Studies, Cyclosporine administration & dosage, Cyclosporine therapeutic use, Disease-Free Survival, Follow-Up Studies, Humans, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents therapeutic use, Infant, Leukemia epidemiology, Life Tables, Middle Aged, Recurrence, Risk, Transplantation, Homologous, Bone Marrow Transplantation, Cyclosporine adverse effects, Immunosuppressive Agents adverse effects, Leukemia therapy
- Published
- 2001
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44. Conventional hematopoietic stem cell transplants from identical or alternative donors are feasible in recipients relapsing after an autograft.
- Author
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di Grazia C, Raiola AM, Van Lint MT, Lamparelli T, Gualandi F, Berisso G, Bregante S, Dominietto A, Mordini N, Bruno B, Frassoni F, and Bacigalupo A
- Subjects
- Adolescent, Adult, Aged, Blood Donors, Female, Hematologic Neoplasms therapy, Humans, Karnofsky Performance Status, Male, Middle Aged, Recurrence, Transplantation, Autologous, Transplantation, Homologous methods, Treatment Outcome, Hematopoietic Stem Cell Transplantation methods, Transplantation, Homologous standards
- Abstract
Background and Objectives: The risk of relapse after autologous bone marrow transplantation (ASCT) is high and is related to the type of malignancy and phase of the disease. The outcome for the patient who relapses after an autologous transplant is poor. Some of these patients achieve a remission with conventional chemotherapy, but it is usually short-lasting. Most of them succumb to the original disease. One further therapeutic possibility is an allogeneic transplant which would confer the potential advantage of a graft-versus-leukemia effect in addition to the lack of tumor contamination of the graft and to a high-dose intensity conditioning regimen., Design and Methods: We have studied the outcome of 31 patients with hematologic malignancies who underwent an allogeneic hematopoietic stem cell transplant (HSCT) after failing an autologous transplant because of relapse (n=29) or persistent aplasia (n=2). The median age at allograft was 36 years (18-55) and the interval from autograft to allograft was 21 months (3-141). The source of stem-cells was unmanipulated bone marrow (n=26) or growth-factor-mobilized peripheral blood (n=5). The donor was an HLA-identical sibling (n=7), or an alternative donor (n=24) (family mismatched n=11, or matched unrelated n=13). The conditioning regimen was cyclophosphamide and thiotepa (n=22), or cyclophosphamide and total body irradiation (n=9) Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine (CyA) + methotrexate (MTX)., Results: Acute GvHD was scored as 0-I, II, or III-IV in 39%, 48%, and 13% of the patients, respectively. Sixteen patients died of transplant-related complications and one of progressive disease. With a median follow-up of 220 days (9-2104) the actuarial 2-year transplant-related mortality (TRM) was 51%, the actuarial relapse risk 37%, the actuarial survival 46%. Fifteen patients (48%) are alive in complete remission, with a median follow-up of 32 months (range 2-71)., Interpretation and Conclusions: These data suggest that patients relapsing after an autotransplant should be screened for potential related or unrelated donors: although TRM remains high there is a definite chance of long-term disease-free survival if these patients are allografted.
- Published
- 2001
45. Fanconi's anemia cells are relatively resistant to H2O2-induced damage.
- Author
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Notaro R, Montuori N, di Grazia C, Formisano S, Rotoli B, and Selleri C
- Subjects
- Adolescent, Adult, Cells, Cultured, Child, Child, Preschool, Erythrocytes metabolism, Female, Hematopoietic Stem Cells metabolism, Humans, Male, Erythrocytes pathology, Fanconi Anemia blood, Fanconi Anemia pathology, Hematopoietic Stem Cells pathology, Hydrogen Peroxide toxicity, Oxidants toxicity, Oxidative Stress
- Abstract
Background and Objective: Fanconi's anemia (FA) is a rare autosomal recessive syndrome characterized by skeletal abnormalities, late onset bone marrow failure and susceptibility to neoplasias. Reduced defense against oxidative stress is thought to be one of the cell damaging mechanisms. We investigated in vitro the effects of oxidative stress on red blood cells (RBC) and on hematopoietic progenitor growth of normal donors and of FA patients., Design and Methods: The effects of hydrogen peroxide (H2O2) on RBC and hematopoietic progenitors were studied in vitro by erythrophagocytosis assay and by hematopoietic progenitor colony assay, respectively., Results: In an erythrophagocytosis assay using normal monocytes, RBC from nine FA patients showed increased binding index (defined as the percentage of monocytes with adherent or phagocytosed RBC) compared to that obtained with RBC from nine normal controls. Upon exposure to H2O2, the binding index of normal RBC increased, while that of FA RBC remained unchanged. In a set of different experiments, H2O2 treatment of peripheral blood mononuclear cells (PBMNC) caused a significant decrease of the number of colonies from circulating progenitor cells in all normal subjects; the inhibition was dose-dependent and direct as proven by using normal purified CD34+ cells. In nine FA patients colony assays from intact cells showed a decreased number of circulating progenitors as compared to normal subjects; however, H2O2 treatment of FA PBMNC did not cause any further decrease of the plating efficiency., Interpretation and Conclusions: Untreated FA cells behave as normal cells after exposure to the toxic effects of H2O2. However, since H2O2 exposure is inoffensive to circulating FA RBC and hematopoietic progenitors, it seems that a selection for cells resistant to further oxidative stress has taken place in the residual hematopoiesis of FA patients. We may surmise that the survival of cells that have suffered from oxidative damage may have increased the risk of their leukemic transformation.
- Published
- 1998
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