Venetoclax Plus Intensified Chemoimmunotherapy as a Bridge to Allogeneic Stem Cell Transplantation in Richter Syndrome: Report of Two Cases

Background: Richter syndrome (RS) represents a major unmet need in the lymphoma field, being refractory to chemoimmunotherapy and targeted agents. The BCL-2 inhibitor venetoclax in combination with dose-adjusted EPOCH-R chemoimmunotherapy showed promising efficacy in patients affected by RS. However, responses were not durable, suggesting the need for further treatment optimization. Methods: Here, we report two cases of RS achieving long-term complete remission with intensified chemoimmunotherapy (Rituximab-G-MALL B-ALL/NHL2002 regimen) plus venetoclax induction, followed by haploidentical hematopoietic stem cell transplant (allo-HSCT). Venetoclax was given continuously for 14 consecutive days after every Rituximab-G-MALL cycle in off-label use. An accelerated venetoclax rump-up schedule was used in both patients to reach the maximal dose. Maximal venetoclax dose was 300 mg and 400 mg in patient 1 and patient 2, respectively. Results: The combined treatment was well tolerated, with no major infective complications or non-hematological toxicities. In both patients, immunosuppression was discontinued within day 180 after transplant with no graft-versus-host-disease flares. Both patients are alive and in continuous complete remission after 60 and 72 months following allo-HSCT. Conclusions: This report supports the feasibility of a combination treatment with BCL-2 inhibitors and intensive chemoimmunotherapy as a bridge to allo-HSCT in RS

Multicenter Experience Using Total Lymphoid Irradiation and Antithymocyte Globulin as Conditioning for Allografting in Hematological Malignancies

A non myeloablative conditioning with total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) was shown to protect against graft-versus-host disease (GVHD). To evaluate the effects of TLI-ATG in a multicenter study, 45 heavily pretreated patients, median age 51, with lymphoid (n = 38) and myeloid (n = 7) malignancies were enrolled at 9 centers. Twenty-eight patients (62%) received at least 3 lines of treatment before allografting, and 13 (29%) had refractory/relapsed disease at the time of transplantation. Peripheral blood hematopoietic cells were from HLA identical sibling (n = 30), HLA-matched (n = 9), or 1 antigen HLA-mismatched (n = 6) unrelated donors. A cumulative TLI dose of 8 Gy was administered from day -11 through -1 with ATG at the dose of 1.5 mg/kg/day (from day -11 through -7). GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. Donor engraftment was reached in 95% of patients. Grade II to IV acute GVHD (aGVHD) developed in 6 patients (13.3%), and in 2 of these patients, it developed beyond day 100. Incidence of chronic GVHD (cGVHD) was 35.8%. One-year nonrelapse mortality was 9.1%. After a median follow-up of 28 months (range, 3-57 months) from transplantation, median overall survival was not reached, whereas median event-free survival was 20 months. This multicenter experience confirms that TLI-ATG protects against GVHD and maintains graft-vs-tumor effects

Outcome of Allogeneic Transplantation for Mature T-cell Lymphomas: Impact of Donor Source and Disease Characteristics

Mature T-cell lymphomas constitute the most common indication for allogeneic hematopoietic cell transplantation (allo-HCT) of all lymphomas. Large studies evaluating contemporary outcomes of allo-HCT in mature T-cell lymphomas relative to commonly used donor sources are not available. Included in this registry study were adult patients who had undergone allo-HCT for anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma (AITL), or peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) between 2008 and 2018. Hematopoietic cell transplantation (HCT) platforms compared were posttransplant cyclophosphamidebased haploidentical (haplo-)HCT, matched sibling donor (MSD) HCT, matched unrelated donor HCT with in vivo T-cell depletion (MUD TCD+), and matched unrelated donor HCT without in vivo T-cell depletion (MUD TCD-). Coprimary end points were overall survival (OS) and progression-free survival (PFS); secondary end points included nonrelapse mortality (NRM), and relapse/progression incidence (RI). A total of 1942 patients were eligible (237 haplo-HCT; 911 MSD; 468 MUD TCD+; 326 MUD TCD-). Cohorts were comparable for baseline characteristics with the exception of higher proportions of patients with decreased performance status (PS) and marrow graft recipients in the haplo-HCT group. Using univariate and multivariate comparisons, OS, PFS, RI, and NRM were not significantly different among the haplo-HCT, MSD, MUD TCD+, and MUD TCD- cohorts, with 3-year OS and PFS of 60%, 63%, 59%, and 64%, respectively, and 50%, 50%, 48%, and 52%, respectively. Significant predictors of inferior OS and PFS on multivariate analysis were active disease status at HCT and decreased PS. AITL was associated with significantly reduced relapse risk and better PFS compared with PTCL-NOS. Allo-HCT can provide durable PFS in patients with mature T-cell lymphoma (TCL). Outcomes of haplo-HCT were comparable to those of matched donor allo-HCT

Analisi sedimentologica e vulcanologica di tre carote provenienti dal Bacino del Marsili (Mar Tirreno Meridionale).

Lo studio e la caratterizzazione delle torbiditi vulcanoclastiche co-genetiche a collassi gravitativi avvenuti sui fianchi di vulcani insulari o costieri è di fondamentale importanza poiché i collassi possono innescare tsunami. Questo è un argomento di studio di fondamentale importanza in particolare in contesti come quello dell’isola di Stromboli, dove, secondo le testimonianze geologiche e storiche sono avvenuti numerosi collassi di versante che potrebbero aver innescato tsunami distruttivi. La tesi ha come argomento principale lo studio sedimentologico e composizionale dei sedimenti campionati in tre carote a gravità prelevate nel tratto terminale del canyon di Stromboli (carota TIR2000-C10-UNICO) e nel Bacino del Marsili (carote VST2002-C13 spezzoni V/VI e VST2002-C14-UNICO), nel Mar Tirreno Meridionale, allo scopo di stabilire se alcune torbiditi vulcanoclastiche contenute in esse possano essere correlate a collassi gravitativi dell’edificio vulcanico di Stromboli. Su queste carote sono state effettuate: descrizione lito-stratigrafica, analisi dei componenti ed analisi chimica della composizione dei vetri. Per la carota del bacino del Marsili (VST2002-C14-UNICO), posta allo sbocco del canyon nella piana batiale, l’interpretazione dei dati non ha permesso di stabilire con certezza se i livelli di sabbie vulcanoclastiche siano effettivamente deposti da torbide co-genetiche a collassi gravitativi di Stromboli o da una generica attività del Canyon di Stromboli. Dalle analisi chimiche è stato stabilito che i prodotti sono compatibili con una provenienza principalmente da Stromboli, Vulcano, Lipari e Salina, con età non superiore ai 30 mila anni. Per la carota posta nel tratto finale del canyon (TIR2000-C10-UNICO), l’origine delle diverse torbiditi è più chiara. Nel livello basale di questa carota (45 cm - 94 cm) ed in quello intermedio (28 cm – 36 cm) c’è una buona probabilità che sia stata registrata la parte finale del collasso del Neostromboli avvenuto all’incirca 6000 anni fa. Nel livello più superficiale, a 12 cm, sembrano essere presenti torbiditi legate a collassi avvenuti dopo l’eruzione di Monte Pilato di Lipari datata 776 d.C.; infatti all’interno del deposito si trovano pomici riconducibili a tale eruzione. Non è stato possibile effettuare una datazione relativa più precisa perché le pomici riolitiche delle eruzioni di Lipari nelle ultime migliaia di anni sono chimicamente indistinguibili, almeno per quanto riguarda la composizione degli elementi maggiori. The identification of volcaniclastic turbidites derived from gravitational collapses is essential because collapses can be linked to tsunami-triggering mechanisms. This is a topic of fundamental importance in particular in contexts such as the island of Stromboli, considering the geological and historical evidence of tsunamis linked to the collapse of the volcano and made even more current if one takes into account its persistent state of activity which has lasted at least since the eighth century AD and that it can accumulate large quantities of material on its slopes. The work concerns the sedimentological and compositional study of three gravity cores sampled in the terminal sector of the Stromboli Canyon (TIR2000-C10-UNICO) and the Marsili Basin (Southern Tyrrhenian Sea) (VST2002-C13-V/VI and VST2002-C14-UNICO), to establish whether the volcaniclastic turbidites stacked within the cores can be correlated to gravitational collapses of the volcanic edifice of Stromboli. On this core the following were carried out: litho-stratigraphic description, analysis of the components and chemical analysis of the composition of the glass shards. By merging the data on the chemistry of the glass shards with the granulometric and componentry data, it was not possible to precisely establish for the core of the Marsili basin (VST2002-C14-UNICO, located at the mouth of the canyon in the bathyal plain) whether the levels of volcaniclastic sands are attributable to turbidity generated by gravitational collapses of Stromboli or by a generic activity of the Stromboli Canyon. Conversely, for the core placed in the final stretch of the Stromboli canyon (TIR2000-C10-UNICO), the basal level (45 cm -94 cm) and the intermediate level show a good probability of correlation with the top of the collapse of Neostromboli (6 ka) while, in the more shallow level at 12 cm, volcanogenic turbidities are possibly linked to collapses that occurred after the 776 AD eruption of Monte Pilato from Lipari. It was not possible to carry out a more precise relative dating because the rhyolitic pumice from Lipari’s eruptions that occurred from 8700 to 1220 AD years ago are chemically indistinguishable, at least as regards the composition of the major elements

Valganciclovir Is Safe and Effective as Pre-Emptive Treatment for CMV Infection in Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract RATIONALE OF STUDY: Despite significant advances in prevention and therapy, cytomegalovirus (CMV) infection still represents an important cause of morbidity and mortality in patients undergoing allogeneic haematopoietic stem cell transplant (HSCT). The standard pre-emptive treatment is based on intravenous administration of Ganciclovir (GCV). Valganciclovir (VGC), the pro-drug formulation of GCV is characterised by an excellent bio availability, making this drug suitable for oral administration. PATIENTS: Since March 2003 all patients treated with reduced (27 patients) or fully ablative (3 patients) conditioning regimens followed by sibling HSCT, were monitored with bi-weekly CMV/PCR and pp65/assays. Overall 15 episodes of CMV positivity were detected in seven patients. Patients resulted positive (3 cells pp65+ or 1000/100000 PCR +) started oral treatment with VGC 900 mg bid, for the first fourteen days, followed by 900 mg q.d. up to at least seven days after assays normalization. The median duration of therapy was 21 days (range 10–21 days). No significant toxicity was observed. All patients had a normalization of CMV/PCR and pp65/assays within fourteen days, with a response rate (RR) of 100%. In two patients the oral VGC therapy was changed to the intravenous administration of Foscavir, because of concomitant neutropenia and acute GvHD. CONCLUSION: Pre-emptive treatment of CMV infection with VGC is safe, feasible and effective. Furthermore, the oral administration of this drug in an outpatient setting, reduces significantly the costs compared with a therapy that needs hospitalization as intravenous Ganciclovir.</jats:p

Unmanipulated, G-CSF Mobilized Peripheral Blood Stem Cells As Graft Source for Non-Myeloablative Haploidentical Transplantation: Fast Engraftment, No Evidence of Graft Rejection, and Low Incidence of Graft-Versus-Host Disease

Abstract Haploidentical bone marrow transplantation using non-myeloablative conditioning and high-dose, post-transplant cyclophosphamide (Cy) has been shown to be a feasible approach for patients lacking an HLA identical donor with acceptable rates of acute and chronic Graft-versus-Host-Disease (GVHD); in the attempt to reduce the associated risk of graft failure and relapse incidence we decided to apply the same conditioning regimen using unmanipulated mobilized peripheral blood stem cells (PBSC). From June 2010 to December 2014, 31 consecutive patients affected by high-risk hematological malignancies, median age 51 years (range 19-70) (3 Acute Myeloid Leukemia, 6 Acute Lymphoblastic Leukemia, 9 Non-Hodgkin Lymphoma, 5 Multiple Myeloma, 2 Myelodysplastic Syndrome, 6 Hodgkin Lymphoma), with no available HLA identical donor (neither related or unrelated) underwent peripheral stem cell transplant from a haploidentical family donor. Disease status at transplant was the following: 13 complete remission (5 patients in 1°CR, 6 patients in 2°CR, 2 patients in 3°CR), 9 partial response (PR), 1 stable disease (SD), 7 progressive disease (PD), and a patient with myelodysplastic syndrome who received the transplant as upfront therapy. Conditioning regimen consisted of cyclophosphamide, fludarabine and TBI followed by infusion of haploidentical PBSC; post-transplant immunosuppression consisted of high-dose Cy on days +3 and +4, tacrolimus and micofenolate mofetile from day +5. A median of 5.7x106 (range 3.8-13.7) CD34+ cells/kg was infused with a median of 2.8x108 (range 0.3-5.4) CD3+ cells/kg. Patients readily engrafted with a median time to absolute neutrophil count ≥500/µL of 17.5 days (range 14-28) in 28/31 patients and a median time to platelet ≥20.000/µL of 21 days (range 11-60) in 27/31 evaluable patients. Three patients died of infection before engraftment, another patient showed myeloid engraftment but never recovered platelet counts and prematurely died of cytomegalovirus (CMV) disease. At a median follow-up of 366 days (16-1682), 16 patients are alive (55%): 13 patients are in CR, the other 3, all affected by Multiple Myeloma, have progressed and are undergoing other treatments, with a cumulative incidence of relapse of 33%. Fifteen patients have died; causes of death included progressive disease in 9 patients (60%) and infections in the remaining 6, with a cumulative transplant related mortality of 18%. CMV reactivation occurred in 15 of 27 patients at risk, at a median time of 34 days (range 22-55) after transplant, resolving with preemptive therapy in 14 patients and causing a fatal infection in 1 heavily pretreated patient. Grade I-II acute GvHD (aGvHD) occurred in 6/28 evaluable patients, with 1-year cumulative incidence of grade I-II aGvHD of 21% and no incidence of grade III-IV GvHD. Mild chronic GvHD (cGvHD) was observed in 3/27 evaluable patients with 1-year cumulative incidence of cGvHD of 11%. Achievement of mixed donor chimerism was rapid: 22/28 evaluable patients showed a CD3+ chimerism &gt;50% by day +28. At day + 84, in 22/26 evaluable patients CD3+ cells chimerism was &gt;90%, while 4/26 showed still a mixed donor chimerism: withdrawal of immunosuppression increased CD3+ chimerism in one patient to 90% at day +360; one patient developed hemolytic anemia and he is under immunosuppression, still a mixed chimera at day +401 while in CR; the other two died from infection at +251 and +361 never reaching the full donor chimerism. No graft failure was observed. Our data show that haploidentical non-myeloablative peripheral blood hematopoietic cell transplantation with high-dose post-transplant Cy is a feasible for patients lacking an HLA identical donor. The use of unmanipulated PBSC with the infusion of a greater number of CD3+ cells allows a rapid and sustained engraftment, reduces the risk of graft failure, does not appear to increase the risk of GVHD with a low/moderate relapse risk. Although the incidence of major infection was low, CMV reactivation remains a critical issues and further studies are needed to clarify recovery of CMV immunity and to reduce the overall treatment related toxicity. Disclosures No relevant conflicts of interest to declare. </jats:sec

Graft-Versus-Lymphoma Effect in Hodgkin’s Disease: A Possible Role in Maintaining a Disease Control.

Abstract Introduction: non-myeloablative and highly immunosuppressive conditioning regimen instead of conventional bone marrow transplantation have been recently developed. The aim of this treatment is to establish a mixed chimerism and to allow the donor cell-mediated graft versus-tumor effect to occur. This is a well known effect in disease like CML and AML and much less investigated in Hodgkin Lymphoma. Patients and methods: from September 2003 to November 2004, 5 pts affected by chemorefractory Hodgkin’s lymphoma, underwent a non-myeloablative conditioning regimen followed by allogeneic peripheral blood stem cell transplantation (PBSCT). Median age was 28 ys (range 26–33), 4 M and 1 F, all pts had failed previous conventional treatment including autologous PBSCT. Conditioning regimen were the following: Fludarabine 30 mg/mq, from day −4 to −2 followed by TBI 2Gy on day 0 in 2 pts; TBI 2Gy alone two month after an autologous PBSCT in 1pt; thiotepa 5mg/kg x2, Fludarabine 30mg/mq, Cyclofosfamide 30 mg/kg in 1pt or Rituximab 600 mg/mq on day −5; fludarabine 30 mg/mq + Cyclofosfamide 30 mg/kg from day −4 to day −3 in the other one. All patients received donor peripheral stem cell infusion on day 0. Prophylaxis of aGVHD was performed with Cyclosporine (6.25 mg/kg) po from day −3 to day +36 followed by a rapid tapering until day +56 and Mycophenolate Mofetil (15mg/kg) po from day 0 to +27. Results: All pts experienced a complete engraftment, obtained a complete response after transplantation and 3/5 them experienced hepatic and/or cutaneous cGvHD. At a median follow-up of 13 months 2/3 pts, who received TBI and/or Fludarabine, are alive after 681 days, 612 days from transplantation and are in CR and SD respectively; both of them had cGvHD; the third one has died at +132 for cerebral hemorrhage. One of the remaining two patients has died at +200 in CR for septic shock after cGvHD, and the last one is still alive in +410 in PD, with no sign of cGvHD. Conclusions: although limited, our data seem to suggest that even in pts affected by Hodgkin’s lymphoma with a chemoresitant disease, the development of cGvHD after a reduced conditioning allogeneic PBSCT, mostly immunosuppressive, seems to be associated with the presence of a graft-versus lymphoma effect able to mediate a good control of the disease.</jats:p

A Cellular Therapy with Haploidentical Peripheral Hematopoietic STEM CELL Transplantation MAY be a Therapeutic Option in Patients with Relapsed Lymphoma with Chemorefractory Disease

Abstract Background: haploidentical hematopoietic stem cell transplant (HSCT) with post-transplant cyclophosphamide (Cy) is a procedure for patients with advanced haematological malignancies lacking an HLA identical donor. Even if several groups reported interesting results about allograft in lymphoma, the current clinical practice doesn't include routinely allogeneic stem cell transplantation in patients with suboptimal response to salvage strategies. A prospective study based on the use of peripheral blood stem cells (PBSC) as graft source was launched at European Institute of Oncology in 2010. The aim of this paper is to report the results of haplo-HSCT in patients with relapsed and refractory lymphoma with detectable disease before transplant. Patients and Methods: between June 2010 and May 2018, 64 have been enrolled in the study at our institute; the updated experience of 35 patients affected by high risk lymphomas is reported.Haploidentical HSCT was performed with G-CSF mobilized PBSC. Conditioning regimen was either non-myeloablative (31 patients) (Cy 14.5 mg/kg/die days -6,-5, fludarabine 30 mg/m2/die days -6 to -2, and 200 cGy Total Body Irradiation day -1), or myeloablative (treosulfane 14 mg/m2/die days -6 to -3 and fludarabine 30 mg/m2/die days -6 to -2). GVHD prophylaxis consisted of post-transplant cyclophosphamide (50 mg/kg day +3 and +4) and mycophenolate and tacrolimus as previously described.Among 35 evaluable patients, 28 (80%) performed haplo-HSCT for refractory/relapsed non-Hodgkin lymphoma; the remaining patients included 7 relapsed and refractory Hodgkin lymphoma. Median age was 52 (19-73), disease status included 13 (37%) complete remission (2 CR1, 11 CR≥2), 9 (26%) partial response (PR), 4 (11%) stable disease (SD), 9 (25%) progressive disease (PD). A median of 5.5 x106(range 2.45 -13.4) CD34+ cells/kg was infused, with a median of 2.8x108(range 0.3-5.4) CD3+ cells/kg. Median lines of previous treatment: 3 (0-7). Results: four deaths due to infections have been recorded before engraftment. Among all 64 evaluable patients, median time to absolute neutrophils ≥500/µL was 18 days (range 12-29), and 23 days (range 11-65) to platelets ≥20.000/µL. Incidence of grade I-II acute GVHD was 22%, with grade III of 2%. Mild chronic GvHD was observed in 7/60 evaluable patients (1-year cumulative incidence: 13 %). Mixed donor chimerism was achieved in all 60 evaluable patients, with CD3+ chimerism &gt;50% at day +28, &gt;90% at day + 84. No graft failure has been recorded. CMV reactivation occurred in 77% of lymphoma patients (27/35 subjects at risk), at a median of 35 days (range 5-50) post-HSCT; pre-emptive therapy was effective in all patients. Regarding the lymphoma population, with a median follow-up of 360 days (6-2,460), 19 patients are alive (54%), 18 of them (51% of the whole series) in CR, while the cumulative incidence of relapse is 25%; when disease status at transplant is considered, the incidence of relapse at 2 years is 4% and 54% for chemo-sensitive and chemo-refractory, respectively (see graphic 2 in figure 1). Overall, 16 patients (45%) died; causes of death were PD in 8 patients (50%), infections in 8 (50%) with a cumulative transplant related mortality of 45%. The 3-year PFS and OS for the all lymphoma patients is 58% and 54%, respectively, with 81% and 66% for patients transplanted in CR/PR and 32 % and 31% for those transplanted in SD/PD (p-value 0,001 Log-rank - graphic 1 in figure 1). Conclusions: Haploidentical T-cell replete PBSC transplantation with high-dose post-transplant Cy is a feasible procedure for high-risk haematological malignancies, with an overall toxicity analogous to HSCT with HLA-identical donors. Despite the small study population, haplo-HSCT seems to be an effective strategy even in patients with active lymphoma before transplant. As previously reported, chemosensitive (CR/PR) patients have a better outcome compared to chemo-refractory cases. However, the latter population still may have a benefit from haplo-HSCT as suggested by our data, thus the cellular therapy strategy should not be discouraged in presence of disease (SD/PD). Our future purpose is to enhance the graft versus lymphoma effect with Natural Killer cells infusions. This option will be soon developed at our hospital within a prospective trial. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. </jats:sec

Non-Myeloablative Haploidentical Transplantation of Unmanipulated, G-CSF Mobilized Peripheral Blood Stem Cells with High Dose Post-Transplant Cyclophosphamide: Fast Engraftment, No Evidence of Graft Rejection and Low Incidence of Graft-Versus-Host-Disease

Abstract Haploidentical bone marrow transplantation using non-myeloablative conditioning and high-dose, post-transplant cyclophosphamide (Cy) has been shown to be a feasible approach for patients lacking an HLA identical donor with acceptable rates of acute and chronic Graft-versus-Host-Disease (GvHD); in the attempt to reduce the associated risk of graft failure and relapse incidence we decided to apply the same conditioning regimen using unmanipulated G-CSF mobilized peripheral blood stem cells (PBSC). From July 2010 to January 2014, 20 patients affected by high-risk hematological malignancies, median age 56 years (range 19-70) (2 Acute Myeloid Leukemia, 5 Acute Lymphoblastic Leukemia, 5 Non-Hodgkin Lymphoma, 3 Multiple Myeloma, 2 Myelodysplastic Syndrome, 3 Hodgkin Lymphoma), with no available HLA identical donor (neither related or unrelated) were enrolled in a prospective clinical protocol at our institution. Disease status at transplant was the following: 10 complete remission (6 patients in 1°CR, 3 patients in 2°CR, 1 patient in 3°CR), 4 partial response (PR), 3 stable disease (SD), 2 progressive disease (PD), and a patient with myelodysplastic syndrome who received the transplant as upfront therapy. Conditioning regimen consisted of cyclophosphamide, fludarabine and TBI followed by infusion of haploidentical unmunipulated mobilized PBSC; post-transplant immunosuppression consisted of high-dose Cy on days +3 and +4, tacrolimus and micofenolate mofetile from day +5. A median of 5.5x106 (range 3.8-13.7) CD34+ cells/kg was infused with a median of 2.8x108(range 0.3-5.4) CD3+ cells/kg in 19/20 evaluable patient: 1 patient was unable to receive the complete conditioning regimen due to rapid worsening of her clinical condition and therefore she was taken out of the study protocol. Patients readily engrafted with a median time to absolute neutrophil count ≥500/µL of 17.5 days (range 14-28) in 17/19 patients and a median time to platelet ≥20,000/µL of 21 days (range 11-53) in 18/19 evaluable patients. One patient died of infection and progressive disease before engraftment, another patient showed myeloid engraftment but never recovered platelet counts and prematurely died of cytomegalovirus (CMV) disease. At a median follow-up of 486 days (12-1297), median OS has not been reached with 13 patients being alive, 8 in CR, 3 in PR and 2 in PD. Causes of death included progressive disease in 3 patients and infections in the remaining 3, with a cumulative transplant related mortality of 15%. CMV reactivation occurred in 12 of 16 patients at risk, at a median time of 34 days (range 22-55) after transplant, resolving with preemptive therapy in 11 patients and causing a fatal infection in 1 heavily pretreated patient. Acute GvHD (aGvHD) occurred in 1 patient, with 1-year cumulative incidence of grade I/II aGvHD of 5.6% (95% CI:8.0-33.4%) and no incidence of grade III/IV GvHD. Mild chronic GvHD (cGvHD) was observed in 2 patients with 1-year cumulative incidence of cGvHD of 8.3% (95% CI:1.2-46.1%). Achievement of mixed donor chimerism was rapid: 16/18 evaluable patients showed a CD3+ chimerism &gt;50% by day +28. At day + 84, in 14/16 evaluable patients CD3+ cells chimerism was &gt;50%, in 6 of them it was &gt;95%. Modulation and withdrawal of immunosuppression increased donor CD3+ chimerism in both of the two remaining patients to 67% and 74% at day +360 and +180, respectively. Notably, no graft failure was observed. Our data show that non-myeloablative haploidentical peripheral blood stem cell transplantation with high-dose post-transplant Cy is a feasible and safe approach for patients lacking an HLA identical donor. The use of unmanipulated, G-CSF mobilized PBSC with the infusion of a greater number of CD3+ cells allows a rapid and sustained engraftment, reduces the risk of graft failure and does not appear to increase the risk of GvHD. Although the incidence of major infection was low, CMV reactivation remains a critical issues and further studies are needed to clarify recovery of CMV immunity and to establish better prophylaxis therapy. Disclosures No relevant conflicts of interest to declare. </jats:sec