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Summary: Haploidentical stem cell transplantation (haploSCT) is becoming a major transplant modality for lymphoma. To assess the effects of donor characteristics, stem cell source and conditioning on outcomes, we identified 474 adults with Hodgkin (HL; 240), peripheral T‐cell (PTCL; 88), diffuse large B‐cell (77), mantle cell (40) or follicular lymphoma (FL; 29), who received haploSCT with post‐transplant cyclophosphamide. Median follow‐up of alive patients was 32 months. On multivariate analysis, acute graft‐versus‐host disease (GVHD) grade 2–4 was lower with offspring donors or bone marrow cells, whereas extensive chronic GVHD was higher in partial response at haploSCT or when using sisters, haploidentical donors beyond first degree, or female donors in male patients. Progression‐free survival (PFS) was better for FL, HL and PTCL, whereas overall survival (OS) was better for HL and PTCL. Complete remission at haploSCT improved PFS and OS whereas these were negatively affected by cytomegalovirus donor positive/recipient positive status. No other donor characteristics (age, gender, human leucocyte antigen mismatch, ABO incompatibility) affected PFS or OS except use of haploidentical donors beyond first degree, which negatively affected OS. PFS and OS are mostly influenced by disease status and lymphoma subtype, supporting the use of any first degree haploidentical family member as a donor. [ABSTRACT FROM AUTHOR]

Cytokine release syndrome (CRS) represents a life‐threatening side effect after haploidentical stem cell transplantation (Haplo‐SCT) with posttransplant cyclophosphamide (PT‐Cy). Factors predictive of CRS development is still a matter of debate. We retrospectively analyzed 102 consecutive patients receiving a bone marrow (BM) (n = 42) or peripheral blood stem cells (PBSC) (n = 60) Haplo‐SCT with PT‐Cy. The two cohorts were similar in main patients' characteristics besides disease type (P =.02). Cumulative incidence of grades 1, 2, and ≥3 CRS was 80%, 52%, and 15% at a median of 2, 4, and 7 days, respectively. Moderate/High‐grade fever (39°‐41°), grade 1 and grade ≥3 CRS occurred more frequently after PBSC relative to BM grafts (68% vs 33%, P =.0005; 87% vs 71%, P =.009; 20% vs 7%, P =.07). Only patients experiencing grade ≥3 CRS had a worse outcome in terms of 1‐year overall survival (OS) and nonrelapse mortality (NRM): 39% vs 80% (P =.002) and 40% vs 8% (P =.005), respectively. By univariate analysis the only factors associated with the increased risk of ≥3 CRS were pretransplant disease status (8% for complete remission, 11% for partial remission, and 38% for active disease, P =.002), HLA‐DRB1 mismatching (57% vs 14%, P =.007), and PBSC graft (P =.07). By multivariable analysis, only pretransplant disease status (hazard ratio, HR: 6.84, P =.005) and HLA‐DRB1 mismatching (HR: 17.19, P =.003) remained independent predictors of grade ≥3 CRS. Only grade ≥3 CRS is clinically relevant for the final outcome of patients receiving Haplo‐SCT with PT‐Cy, is more frequent after a PBSC graft and is associated with pretransplant active disease and HLA‐DRB1 mismatching. [ABSTRACT FROM AUTHOR]

Transplantation from haploidentical donors is widely used, with progressive reduction of cord blood (CB) as alternative donor. The paper by Matsuda and colleagues, the largest analysing the outcome in non‐remission acute myeloid leukaemia (AML) transplanted with haploidentical donor or CB, suggests that CB is still a viable option when considering allogeneic transplantation for advanced AML. Commentary on: Matsuda et al. Comparison of transplant outcomes between haploidentical transplantation and single cord blood transplantation in non‐remission acute myeloid leukaemia: A nationwide retrospective study. Br J Haematol. 2023;201:106–113. [ABSTRACT FROM AUTHOR]

The article focuses on the survival and relapse rate associated with immunotherapy donor lymphocyte infusion (DLI) which is used for allogeneic haematopoietic stem cell transplantation (Allo-HSCT). It talks about the Allo-HSCT being used for treatment in patients with haematological malignancies. It tells about the non-relapse mortality (NRM) rate being low for Allo-HSCT.

Objectives: T‐cell–replete haploidentical stem cell transplantation (Haplo‐SCT) with post‐transplant cyclophosphamide (PT‐Cy) is at high risk of invasive fungal infections (IFI), and anti‐mold–active drug is required for primary antifungal prophylaxis (PAP) according to international guidelines. No data are available on the efficacy of caspofungin as PAP in this setting. Methods: Here, we report our retrospective experience with 103 consecutive patients treated with caspofungin as PAP after Haplo‐SCT. Caspofungin was administered only during the pre‐engraftment phase. Results: Hundred‐day cumulative incidence of proven‐probable IFI (PP‐IFI) was 8.7% and median day of onset was 19 post‐SCT. No patient died of PP‐IFI, and overall survival (OS) and non‐relapse mortality (NRM) hazard ratio (HR) for patients experiencing IFI were 1.02 (P = 0.9) and 0.7 (P = 0.7), respectively. Three‐year overall survival (OS) and 1‐year non‐relapse mortality (NRM) were 55% and 19%, respectively. By univariate analysis, duration of neutropenic phase and partial remission pre‐transplant disease status were associated with increased incidence of IFI, but were not confirmed by multivariate analysis. Conclusion: In summary, PAP with caspofungin is an effective strategy for preventing IFI in the context of Haplo‐SCT with PT‐Cy. Further efforts are required in order to identify more potent strategies able to avoid the occurrence of breakthrough infections. [ABSTRACT FROM AUTHOR]

Background: The treatment of patients with Hodgkin lymphoma (HL) who develop disease progression after undergoing allogeneic stem cell transplantation (allo-SCT) remains challenging.Methods: The authors assessed outcomes in 184 adult patients with HL who developed disease recurrence or progression after a matched related or unrelated allo-SCT at European Society for Blood and Marrow Transplantation-participating centers between 2010 and 2014.Results: Eighty patients who received brentuximab vedotin (BV) salvage therapy were compared with 104 patients who did not. Patients in the BV group were younger (median age of 30 years vs 34 years) and were more likely to receive pretransplant BV (65% vs 46%) or posttransplant donor lymphocyte infusion (66% vs 33%). The 2 groups otherwise were comparable. Patients in the BV group received a median of 6 doses of posttransplant BV, resulting in a complete remission rate of 29%, a partial response rate of 45%, and a stable disease rate of 26%. Response to BV after allo-SCT did not appear to be affected by receipt of pretransplant BV. Despite a longer median follow-up for surviving patients in the BV group (33 months vs 23 months; P<.001), approximately 34% of the original BV cohort were alive and in CR at the time of last follow-up versus 18% in the group that did not receive BV (P=.003). The use of BV before donor lymphocyte infusion was found to be associated with the highest probability of being alive and in CR (40%) at the time of last follow-up. Salvage BV appeared to have no effect on chronic graft-versus-host disease or 1-year overall survival from the time of disease recurrence after allo-SCT (76% vs 67%).Conclusions: BV is a safe and effective salvage therapy for patients with HL who develop disease recurrence or progression after undergoing allo-SCT, even after prior exposure to BV. [ABSTRACT FROM AUTHOR]

Abstract: Background: Invasive fungal infections (IFI) represent a common side effect of allogeneic hematopoietic stem cell transplant (allo‐SCT), resulting in increased non relapse mortality (NRM) and reduced overall survival (OS) rates. Seventy‐five days of Fluconazole 400 mg/d represents the standard primary antifungal prophylaxis (PAP) after allo‐SCT, especially for low‐risk transplants. However, the ideal dosage of fluconazole has never been tested. Methods: Here, we report the experience of our institution on 113 consecutive patients receiving an allo‐SCT from a HLA identical sibling between 1999 and 2015, where PAP consisted of fluconazole 100 mg/d only during the pre‐engraftment phase. At the time of transplant, all patients were considered at low‐risk for mold infection according to ECIL‐5 guidelines. Results: Cumulative incidence of possible‐probable‐proven IFI was 11.7%, while proven‐probable (PP‐IFI) occurred in 5.5% of patients by day 100 post transplant. Of note, only 1 patient developed invasive Candidiasis due to a non‐albicans strain and stool‐screening tests were negative for colonization by Candida albicans species. The incidence of 1‐year acute and 2‐year chronic graft‐versus‐host‐disease (GVHD) was 30% and 45%, respectively. Three‐year OS and 1‐year NRM were 53% and 11.3%, respectively. Conclusion: In summary, fungal prophylaxis with fluconazole 100 mg/d results in very low incidence of PP‐IFI, GVHD and NRM in low‐risk allo‐SCT. [ABSTRACT FROM AUTHOR]

Background: Incidence of graft-versus-host disease (GVHD) in haploidentical bone marrow (BM) transplants using posttransplantion cyclophosphamide (PT-Cy) is low, whereas GVHD using mobilized peripheral blood stem cells (PBSC) ranges between 30% and 40%.Methods: To evaluate the effect of stem cell source in haploidentical transplantation with PT-Cy, we analyzed 451 patients transplanted for acute myeloid leukemia or acute lymphoblastic leukemia reported to the European Society for Blood and Marrow Transplantation.Results: BM was used in 260 patients, and PBSC were used in 191 patients. The median follow-up was 21 months. Engraftment was lower in BM (92% vs 95%, P < 0.001). BM was associated with a lower incidence of stage II-IV and stage III-IV acute GVHD (21% vs 38%, P ≤ .01; and 4% vs 14%, P < .01, respectively). No difference in chronic GVHD, relapse, or nonrelapse mortality were found for PBSC or BM. The 2-year overall survival (OS) was 55% versus 56% (P = .57) and leukemia-free survival (LFS) was 49% versus 54% (P = .74) for BM and PBSC, respectively. On multivariate analysis, PBSC were associated with an increased risk of stage II-IV (hazard ratio [HR], 2.1; P < .001) and stage III-IV acute GVHD (HR, 3.8; P < .001). For LFS and OS, reduced intensity conditioning was the only factor associated with treatment failure (LFS: HR, 1.40; P = .04) and relapse (HR, 1.62; P = .02).Conclusion: In patients with acute leukemia in first or second remission receiving haploidentical transplantation with PT-Cy, the use of PBSC increases the risk of acute GVHD, whereas survival outcomes are comparable. Cancer 2018;124:1428-37. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Summary: Brentuximab vedotin (BV) is an anti‐CD30 antibody‐drug conjugate. Preliminary data suggest that BV might improve outcomes after allogeneic stem cell transplantation (SCT) for Hodgkin lymphoma (HL) when used as pre‐transplant salvage therapy. Between 2010 and 2014, 428 adult patients underwent an allogeneic SCT for classical HL at participating centres of the European Society for Blood and Marrow Transplantation. We compared the outcomes of 210 patients who received BV prior to allogeneic SCT with that of 218 patients who did not receive BV. The median follow‐up for survivors was 41 months. Patients in the BV group were more heavily pre‐treated (median pre‐allograft treatment lines: 4 vs. 3). The two groups were comparable in terms of disease status, performance status, comorbidities, prior autologous SCT, type of donor, conditioning and in vivo T cell depletion. In multivariate analysis, pre‐allograft BV had no impact on acute graft‐versus‐host disease (GVHD), non‐relapse mortality, cumulative incidence of relapse, progression‐free survival or overall survival (OS), but significantly reduced the risk of chronic GVHD (hazard ratio = 0·64; 95% confidence interval = 0·45–0·92; P < 0·02). Older age, poor performance status, use of pre‐transplant radiotherapy and active disease at SCT adversely affected OS. Patients allografted for HL after prior exposure to BV do not have a superior outcome after allogeneic SCT except for a lower risk of chronic GVHD. However, BV may improve the outlook of allogeneic SCT by helping otherwise refractory patients to achieve a more favourable disease status, facilitating allotransplant success. [ABSTRACT FROM AUTHOR]

BACKGROUND The presence of human leukocyte antigen donor-specific antibodies (DSAs) increases the risk of graft failure in T-cell-replete haploidentical hematopoietic stem cell transplantation (haplo-HSCT) CASE REPORT A 49-year-old female with high-risk acute myeloid leukemia in first complete remission received a haplo-HSCT from her daughter. Pretransplant recipient screening examination showed high DSAs levels against unshared class I leukocyte antigens. RESULTS The patient underwent a desensitization program consisting of plasma exchange (PEX), polyvalent intravenous (IV) immunoglobulins, and IV tacrolimus and mycophenolate mofetil (MMF). This protocol resulted in the disappearance of the DSA anti HLA B41. Engraftment was prompt with stable full donor chimerism. CONCLUSIONS This case report suggests that the adopted scheme is safe for reducing DSA levels and facilitating donor engraftment in patients scheduled for haplo-HSCT. [ABSTRACT FROM AUTHOR]

Classical Hodgkin's lymphoma ( cHL), a distinct disease entity with characteristic clinical and pathological features, accounts for approximately 10% of all malignant lymphomas. cHL can be considered a prototype model for how the tumour microenvironment influences cancer pathogenesis. Cellular components of the cHL microenvironment express molecules involved in cancer cell growth and survival, such as CD30L or CD40L. Moreover, several signal transduction pathways that are critical for the proliferation and survival of neoplastic Hodgkin Reed-Sternberg ( HRS) cells, including NF-κB, JAK-STAT, PI3K-AkT and ERK, are deregulated in cHL. Although most patients can be cured with modern treatment strategies, approximately a quarter experience either primary or secondary chemorefractoriness or disease relapse, thus requiring novel treatments. Preclinical and clinical evidence has elucidated a complex crosstalk between malignant HRS cells and the reactive cells of the microenvironment, which suggests that novel therapeutic approaches capable of targeting HRS cells along with reactive cells might overcome chemorefractoriness. In the near future, these novel therapies will also be tested in chemosensitive patients, to reduce the long-term toxicity of chemo-radiotherapy. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BACKGROUND Alternative donors, such as unrelated umbilical cord blood (UCB) and related haploidentical (haplo) donors, are more and more frequently searched for and used for patients who are candidates for allogeneic hematopoietic stem cell transplantation but are without a suitable related or unrelated donor. The aim of the current retrospective study was to compare the outcome of patients after haplo and UCB grafts prepared using a nonmyeloablative conditioning regimen. METHODS A total of 150 adult patients with high-risk hematologic diseases who underwent allogeneic hematopoietic stem cell transplantation from alternative donors at 2 centers (Paoli-Calmettes Institute [Marseille, France] and Humanitas Cancer Center [Milan, Italy]) were analyzed. Sixty-nine patients had haplo donors and 81 patients had UCB donors. RESULTS The cumulative incidence of nonrecurrence mortality at 1 year was 23% in the UCB group versus 17% in the haplo group ( P = .39). The incidence of grade 2 to 4 acute graft-versus-host disease and extensive chronic graft-versus-host disease in the UCB group versus the haplo group was 52% versus 29% ( P = .05) and 12% versus 6% ( P<.0001), respectively. The overall survival rate at 2 years was 45% in the UCB group (95% confidence interval [95% CI], 34%-56%) versus 69% in the haplo group (95% CI, 58%-80%) ( P = .10). The progression-free survival rate at 2 years was 36% in the UCB group (95% CI, 25%-47%) versus 65% in the haplo group (95% CI, 53%-77%) ( P = .01). CONCLUSIONS The results of the current study suggest that for patients with high-risk hematological diseases without a related or unrelated donor, haploidentical transplants are a promising alternative option that deserves further investigation. Cancer 2015;121:1809-1816. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

The article discusses the study on non-myeloablative (NMA) peripheral blood stem cells (PBSC) human leucocyte antigen (HLA)-haploidentical Allo-HSCT (Haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy) on patients aged 50 and above. Topics discussed include finding of low-incidence of chronic graft-versus-host disease (GVHD), feasibility of NMA Haplo-SCT with PT-Cy platform for older patients, and use of PBSC does not result in increased GVHD incidence.

Purpose: To evaluate the dosimetric consequences of inaccurate isocenter positioning during treatment of total marrow (lymph-node) irradiation (TMI-TMLI) using volumetric modulated arc therapy (VMAT). Methods: Four patients treated with TMI and TMLI were randomly selected from the internal database. Plans were optimized with VMAT technique. Planning target volume (PTV) included all the body bones; for TMLI, lymph nodes and spleen were considered into the target, too. Dose prescription to PTV was 12 Gy in six fractions, two times per day for TMI, and 2 Gy in single fraction for TMLI. Ten arcs on five isocenters (two arcs for isocenter) were used to cover the upper part of PTV (i.e., from cranium to middle femurs). For each plan, three series of random shifts with values between -3 and +3 mm and three between -5 and +5 mm were applied to the five isocenters simulating involuntary patient motion during treatment. The shifts were applied separately in the three directions: left-right (L-R), anterior-posterior (A-P), and cranial-caudal (C-C). The worst case scenario with simultaneous random shifts in all directions simultaneously was considered too. Doses were recalculated for the 96 shifted plans (24 for each patient). Results: For all shifts, differences <0.5% were found for mean doses to PTV, body, and organs at risk with volumes >100 cm3. Maximum doses increased up to 15% for C-C shifted plans. PTV covered by the 95% isodose decreased of 2%-8% revealing target underdosage with the highest values in C-C direction. Conclusions: The correct isocenter repositioning of TMI-TMLI patients is fundamental, in particular in C-C direction, in order to avoid over- and underdosages especially in the overlap regions. For this reason, a dedicated immobilization system was developed in the authors' center to best immobilize the patient. [ABSTRACT FROM AUTHOR]

BACKGROUND: The optimal combination of fludarabine, busulfan, and antithymocyte globulin (ATG) for reduced-intensity conditioning (RIC) transplantation has not been established. ATG plays a pivotal role in the prevention of graft-versus-host disease (GvHD), but it is associated with a higher relapse rate and an elevated incidence of infections when high doses are used. METHODS: The authors retrospectively compared 2 different doses of ATG combined with fludarabine and busulfan in 229 adult patients who underwent transplantation at their institution. ATG was administered over 1 day (FBA1) or over 2 days (FBA2) at a daily dose of 2.5 mg/kg. RESULTS: There were 124 patients in the FBA2 cohort and 105 patients in the FBA2 cohorts. Patients in the FBA2 cohort were older and more frequently underwent transplantation from an unrelated donor; 93% of patients in the FBA2 cohort received intravenous busulfan versus only 5% in the FBA1 cohort. The incidence of grade 2 through 4 acute GvHD was 23% in the FBA2 cohort versus 42% in the FBA1 cohort ( P = .002); the incidence of grade 3 through 4 acute GvHD was 10% versus 23%, respectively ( P = .006); and the incidence of chronic GvHD was 35% versus 69%, respectively ( P < .0001). The 2-year rates of overall survival, nonrelapse mortality, and relapse/progression for the FBA1 and FBA2 cohorts were 65% versus 67%, respectively ( P = .99), 20% versus 19%, respectively ( P = .61), and 30% versus 19%, respectively ( P = .09). The results were confirmed in multivariate analysis. CONCLUSIONS: The use of ATG at a dose of 5 mg/kg was correlated significantly with reduced incidence and severity of GvHD without impairing disease control. Taken together, the current results suggest that this conditioning represents a step forward in the optimization of RIC. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: The optimal intensity of reduced-intensity conditioning (RIC) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains uncertain. METHODS: In this centrally randomized phase 2 study, the authors compared 2 different strategies of RIC. In total, 139 patients (median age, 54 years; range, 21-65 years) with hematologic malignancies underwent allo-HSCT from a human leukocyte antigen-identical sibling after conditioning combining fludarabine with either busulfan and rabbit antithymocyte-globulin (BU-rATG) (n = 69) or total body irradiation (TBI) (n = 70). Postgraft immunosuppression consisted of cyclosporin A in all patients with the addition of mycophenolate-mophetil after TBI. RESULTS: The median follow-up was 54 months (range, 26-88 months). One-year overall survival rate was identical in both groups. Four patients experienced graft-failure after TBI. The incidence of grade 2 through 4 acute graft-versus-host-disease was greater after BU-rATG than after TBI (47% vs 27%; P = .01), whereas no difference was observed with chronic graft-versus-host-disease. The BU-rATG group had a higher objective response rate (65% vs 46%; P = .05) and a lower relapse rate (27% vs 54%; P < .01). However, the nonrelapse mortality rate was higher after BU-rATG than after TBI (38% vs 22%; P = .027). At 5 years, the overall and progression-free survival rates were 41% and 29%, respectively, and did not differ statistically between groups. A detrimental effect on some parameters of quality of life was more pronounced after BU-rATG, but recovery was identical in both groups. The mean total cost per patient, including the cost to treat disease progression post-transplantation, did not differ statistically between groups. CONCLUSIONS: Five years after transplantation, the BU-rATG regimen was associated with greater disease control. However, because of the higher nonrelapse mortality rate, this did not translate into better overall or progression-free survival. Cancer 2013. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess the results of allogeneic stem cell transplantation (allo-SCT) after reduced-intensity conditioning (RIC) from matched related donors (MRD) and unrelated donors (URD) in 40 patients with high-risk multiple myeloma (MM) in a single centre. Seventeen (43%) (Group 1) and 23 patients (57%) (Group 2) had URD and MRD, respectively. Thirty-nine patients (98%) received one or more autologous transplantation. The median follow-up was 22 months (1-49). None of our patient experienced a graft rejection. The cumulative incidence of grade II-IV acute GVHD was higher (47%) for the URD vs. (17%) for the MRD ( P = 0.092). The cumulative incidence of chronic GVHD was no different between the two groups (24% vs. 30%, respectively). At 2 yr, the TRM probabilities were lower in the unrelated group 12% vs. 22% in the related group ( P = 0.4). Also at 2 yrs, for patients receiving unrelated transplantation overall and progression-free survivals, 59% and 42%, respectively compared to patients with related donor transplantation, 66% and 44% ( P = 0.241). In conclusion, these results suggest that URD in MM is feasible. The small number of patients with URD emphasizes the need to delineate indications and perform prospective protocols. [ABSTRACT FROM AUTHOR]

The article provides information on a study which determined the prognostic value of 18-fluoro-deoxyglucose (FDG)-positron emission tomography (PET) in patients with chemosensitive Hodgkin lymphoma (HL) or aggressive non-Hodgkin lymphoma (NHL) before reduced-intensity conditioning (RIC) allogenic autologous stem cell transplantation (alloSCT). A review of the related literature on RIC regimens is offered. Data collection was done between May 2001 and December 2007. Findings of the study are discussed in detail.

This retrospective study evaluated whether early 2-[fluorine-18]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) after two cycles of salvage chemotherapy (PET2) could predict survival after high-dose chemotherapy (HDC). Twenty-four Hodgkin lymphoma (HL) patients were included. PET2 was negative in 58% and positive in 42% of patients. Ninety per cent of patients (9/10) with positive PET2 relapsed after HDC while all but one patient with negative PET2 maintained a complete remission. The 2-year progression-free survival was 93% vs. 10% for patients with negative and positive PET2, respectively ( P < 0.001). This study shows that interim PET can predict the outcome after high-dose chemotherapy in HL patients. [ABSTRACT FROM AUTHOR]

Background: We analysed the feasibility and efficacy of allogeneic stem cell transplantation (allo-SCT) with reduced-intensity conditioning (RIC) in patients with refractory or progressive Hodgkin's disease (HD) after high-dose chemotherapy (HDCT). Patients and methods: Fourteen patients with HD received allo-SCT with RIC: eleven patients had a human leucocytes antigen-identical related donor and three a matched unrelated donor. Six had chemoresistant disease and eight had chemosensitive one at the time of transplantation. All patients received a fludarabine-based RIC. Results: All patients engrafted and full donor chimerism was achieved in all patients. Grade II acute graft-vs.-host disease (GvHD) developed in six of the 14 patients (43%). Chronic GvHD developed in eight of the 13 patients (61%). There was neither early nor late treatment-related mortality (TRM). With a median follow-up of 21 months (range 3–74), 10 of the 14 patients were alive (71%). Estimated overall survival at 1 and 2 yr was 93% and 73%, respectively, for the whole population, 83% and 44% respectively for patients with chemoresistant disease and 100% for those with chemosensitive disease. Estimated progression-free survival at 1 yr was 36%; 62.5% for chemosensitive patients and 0% for those with chemoresistant disease. Conclusions: In conclusion, allo-SCT with fludarabine-based RIC is a feasible procedure, without TRM in HD patients relapsed and refractory after HDCT. Even if several questions are still open, this approach should proposed for these poor prognosis patients. [ABSTRACT FROM AUTHOR]

Extracorporeal photochemotherapy (ECP) has been progressively introduced into the treatment of both acute and chronic graft-versus-host disease (cGvHD) over the last decade. Nevertheless, its mechanisms of action, as well as the optimal treatment schedule, have not yet been defined. We retrospectively analyzed 25 patients with cGvHD unresponsive to conventional treatments who underwent ECP from 1997 until 2005. The impact of various factors (such as treated and infused nucleated cells, time from transplantation and cGvHD onset, and time from cGvHD and ECP treatment) on the probability of no response to ECP was therefore investigated. A positive response to ECP was achieved in 80% of the patients, after a median of 19 ECP treatments (with a range of 8–38). Eighteen out of the 20 patients responsive to the treatment maintained their response for a median of 30 months. We mainly focused on clinical response and yield composition. The analysis on mononuclear cell (MNC) dose suggested that an increase of MNC dose/kg b.w. (body weight) induced a decrease in the odds of treatment failure, and that, if the MNC dose infused was at least 100 × 106/kg b.w. per ECP treatment, a more positive and longer-lasting response was achieved. Moreover, the mean dose of treated and infused monocytes × 106/kg b.w./ECP did not account for a clear dose-related effect. These findings may eventually result in a more patient-tailored approach to ECP. Prospective multicenter trials should be designed to investigate the real impact of MNC dose on ECP responsiveness. [ABSTRACT FROM AUTHOR]

Our goal was to optimize use of granulocyte colony-stimulating factor (G-CSF) after high-dose chemotherapy and autologous peripheral blood stem-cell transplantation in lymphoma patients, limiting G-CSF administration to patients infusing a suboptimal CD34+ cell number. Of 124 consecutive patients with histologically proven Hodgkin's and non-Hodgkin's lymphoma from January 2001 to June 2004, 60 patients (group 1) given ≥5 × 106/kg CD34+ cells received no G-CSF; 64 patients (group 2) given ≤5 × 106/kg CD34+ cells received G-CSF from day +5 after stem-cell reinfusion. The median times to reach 0.5 × 109/L and 1.0 × 109/L neutrophils were, respectively, 3 and 4 d shorter in G-CSF group and this difference was statistically significant ( P = 0.0014; P = 0.0001). In terms of antibiotic and antimycotic requirements, gastrointestinal toxicity, days of hospitalization, and transfusion requirements, no differences were demonstrated between the two groups. No statistically significant difference was demonstrated for the total number of febrile episodes (52 for group 1; 53 for group 2; P = 0.623) and the median number of febrile days (2 d for both groups). Myeloid reconstitution values for both groups agree with published results for autotransplanted patients treated with G-CSF from 7 to 14 d. Also, major clinical events, antibiotic, antimycotic, and transfusion requirements, and hospital stay were similar to published findings. Our data suggest that G-CSF administration can be safely optimized, used only for patients infused with a suboptimal CD34+ cell dose. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about the high incidence of hemostatic interference in cancer patients treated with FOLFOX regimen and concomitant minidose of warfarin.

A letter to the editor is presented in response to the article "Successful treatment of thrombotic microangiopathy after haematopoietic stem cell transplantation with rituximab," by W. Y. Au and colleagues.

We designed a prospective study to evaluate the feasibility and efficacy of tandem high-dose chemotherapy (HDCT) in the treatment of refractory or relapsed Hodgkin's lymphoma (HL). Thirty-two patients were treated with salvage chemotherapy (IGEV, ifosfamide, gemcitabine, and vinorelbine) and chemo-sensitive patients received a first HDCT course with melphalan 200 mg/m(2) (MEL200) and a second BEAM course. The median time interval between the two HDCT courses was 66 days. The median number of reinfused CD34(+) cells was 4.7 x 10(6)/kg after MEL200 and 5.8 x 10(6)/kg after BEAM. The hematological reconstitution after both HDCT courses did not differ. No grade III or IV renal, hepatic, lung, cardiac, and neurological toxicity was observed. Severe (grade III and IV) oral mucositis was the most prominent complication affecting 60 and 50% of patients after MEL200 and BEAM, respectively. Fever of unknown origin occurred in 65 and 70% of patients after MEL200 and BEAM, respectively. One patient died from septic shock during the aplasia period following BEAM. In an intention-to-treat analysis, the overall response rate increased after each stage of protocol, ranging from 47% to 65% and 75% after IGEV, MEL200, and BEAM, respectively. Tandem HDCT is feasible and effective in patients with relapsed or refractory HL., ((c) 2006 Wiley-Liss, Inc.)

Patients with a central venous catheter (CVC) undergoing high-dose chemotherapy (HDC) followed by peripheral-blood stem-cell transplantation (PBSCT) for malignancies are at high risk of thrombosis, but the use of anti-coagulant prophylaxis remains debatable in this setting of patients. We analyzed the efficacy and the safety of minidose warfarin in 228 patients in whom CVCs had been placed and who had received 292 HDC courses of therapy. The catheters remained in place for a mean of 173 (range 40-298) days. All patients received prophylactic oral warfarin in the fixed dose of 1 mg/day starting on the day of CVC insertion. Prophylaxis was interrupted during aplasia when platelet counts fell below 50,000/dL. There were no toxic deaths related to the prophylaxis. Overall there were 4 thrombotic events. Three occurrences were directly related to the catheter, while the remaining event was a deep saphenous-vein thrombosis. A number of potential predictive factors were analyzed for their impact on thrombotic events without finding any significant correlation. Four episodes of bleeding occurred, with each of these individuals having a normal INR but a platelet count below 50,000/dL. Minidose warfarin is effective and safe to use for preventing thrombotic events in this setting of patients., ((c) 2005 Wiley-Liss, Inc.)

Primary mediastinal B-cell lymphoma (PMBCL) is a clinicopathological entity with aggressive behavior. Retrospective evaluation suggests the need for intensive chemotherapy programs. From 1997 to February 2003, a total of 11 cases of previously untreated PMBCL with sclerosis were treated at our institution with 5 courses of intensified CHOP (ICHOP) regimen and mediastinal irradiation. Three patients were submitted to high-dose chemotherapy with peripheral-blood stem-cell support, followed by radiotherapy, because of intermediate-risk age-adjusted International Prognostic Index at diagnosis. After a median follow up of 30 months, all patients but one are in continuous complete remission (CR), and overall survival is 100%.

The aim of this retrospective study was to investigate the feasibility of high-dose therapy (HDT) followed by peripheral blood stem cell transplantation (PBSCT) in elderly patients with hematological malignancies. From April 1998 to November 2001, 40 elderly patients (defined as > or =60 years) with non-Hodgkin's lymphoma (12 patients) and multiple myeloma (28 patients) were evaluated. Seven lymphoma and one myeloma patients were in complete remission (CR), 27 in partial remission (PR), two had stable disease (SD), and three progressive disease (PD). The median age was 65 years (range 60-71). Thirty-nine patients were mobilized with chemotherapy plus granulocyte-colony stimulating factor (G-CSF) and one with G-CSF alone. Patients received HDT including melphalan alone in 32 cases or combined with other drugs in six and BEAM in two. The median number of collected CD34(+) cells was 12.4 x 10(6)/kg (range 2.0-68.9). The median number of re-infused CD34(+) cells was 9.9 x 10(6)/kg (range 2.0-68.9). All patients engrafted after PBSC and the median time to neutrophil recovery (N > 500/micro l) and platelet recovery (PLT > 20,000/micro l) was 8 days (range 5-18) and 6 days (range 5-18), respectively. Nonhematological toxicity was mild and no patient died from transplant-related toxicity (TRM). Median duration of hospitalization was 18 days (range 12-24). To date, 32 patients are alive and eight died from disease progression at a median follow-up interval of 24 months. HDT supported by PBSC is a feasible procedure in selected elderly patients, and an age of more than 60 years should not be considered a contraindication for HDT., (Copyright 2003 Wiley-Liss, Inc.)