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Relapse rates following allogeneic stem cell transplantation for acute myeloid leukemia remain unacceptably high and a major cause of death. Maintenance therapies post-transplant administered either to patients with impending relapse or at high risk of relapse could present a strategy to improve survival and overall outcomes. With the increasing use of molecular and genomic characterization of the disease, more novel therapies became available as maintenance strategies. These options were, however, hindered by excessive toxicities, mostly hematologic, especially with the use of myeloablative conditioning regimens. Several key questions have also emerged including the efficacy of these therapies, the duration of maintenance, as well as the potential modulation of the graft and the immune microenvironment. These issues are further complicated by the paucity of well-designed prospective randomized clinical trials evaluating these agents. Future directions in this field should include better risk stratification and patient selection based on assays of minimal residual disease, as well as the incorporation of novel targets and pathways of leukemogenesis. In this article, we highlight the current evidence behind the use of post-transplant maintenance therapy, the optimal patient and disease selection, as well as the challenges faced by these strategies in an area that remains quite controversial. We will focus on therapies targeting leukemia stem cells that directly or indirectly modulate the allografted immune microenvironment and augment the graft-versus-leukemia impact.

Background: Invasive fungal infections (IFI) following allogeneic stem cell transplant (allo-HCT) are associated with high morbidity and mortality. Primary prophylaxis using voriconazole has been shown to decrease the incidence of IFI. Methods: We conducted a retrospective analysis at the Bone Marrow Transplant (BMT) unit of the American University of Beirut including 195 patients who underwent allo-HCT for hematological malignancies and received voriconazole as primary prophylaxis for IFI. The primary endpoints were based on the incidence of IFI at day 100 and day 180, and the secondary endpoint based on fungal-free survival. Results: For the study, 195 patients who underwent allo-HCT between January 2015 and March 2021 were included. The median age at transplant was 43 years. Of the patients, 63% were male, and the majority of patients were diagnosed with acute myeloid leukemia (AML) (60%). Voriconazole was given for a median of 90 days and was interrupted in 20 patients. The majority of IFI cases were probable invasive aspergillosis (8%). The incidence of IFI including proven, probable and possible IFI was 34%. The incidence of proven and probable IFI was 5% were 8%, respectively. The incidence of proven-probable (PP-IFI) was 5.1% at day 100 and 6.6% at day 180. The majority of PP-IFI cases were invasive aspergillosis (8%). A univariate analysis of patients, transplant characteristics and IFI showed a significant correlation between the type of donor, disease status before transplant, graft-versus-host disease prophylaxis used and incidence of IFI. Only disease status post-transplant showed a significant correlation with fungal-free survival in the multivariate analysis. Conclusion: Primary prophylaxis with voriconazole in allo-HCT is associated with a low incidence of IFI. More studies are required to compare various antifungal agents in this setting.

BackgroundThe Coronavirus Disease 2019 (COVID-19) was declared a pandemic by WHO in March 2020. The first case of COVID-19 was identified in Lebanon on the 21st of February 2020, amid a national economic crisis. As the numbers of cases increased, ICU admissions and mortality rose, which led hospitals across Lebanon to take certain safety measures to contain the virus. The Naef K. Basile Cancer Institute (NKBCI) at the American University of Beirut Medical Center handles oncology outpatient visits and outpatient treatment protocol infusions. The aim of this study is to evaluate the efficacy of the safety measures put forth by the NKBCI early in the pandemic.MethodsOncology patients are amongst the immunosuppressed population, who are at greatest risk of contracting COVID-19 and consequently suffering its complications. In this manuscript, we evaluated the precautionary measures implemented at the NKBCI of AUBMC from March 1st to May 31st of 2020, by surveying oncology patients on the telephone who had live and virtual appointments in both the oncology outpatient clinics and infusion unit. We conducted a prospective study of 670 oncology patients who had appointments at the NKBCI during this period and used their answers to draw responses about patient satisfaction towards those safety measures.ResultsOur results involved 387 responses of oncology patients who visited the NKBCI during the period of March 1st to May 31st of 2020. 99% of our respondents gave a rating of good to excellent with these new measures. The option of online consultation was given to 35% in the hematology group compared to 19% in those with solid tumors (p=0.001). From the total, 15% of patients opted for the telemedicine experience as a new implemented strategy to provide patient-centered medical care. Of this group of patients, 22% faced problems with connectivity and 19% faced problems with online payment.ConclusionNKBCI was competent in following the WHO guidelines in protecting the oncology patient population. Feedback collected from the surveys will be taken into account by the committee of the NKBCI to develop new safety measures that can better control viral spread while providing patient-centered medical care.

We compared transplant outcomes of 708 acute myeloid leukemia (AML) patients receiving haploidentical allogeneic hematopoietic-cell transplantation using thiotepa/busulfan/fludarabine (TBF) conditioning with posttransplant cyclophosphamide (ptCy), to 2083 patients receiving matched unrelated donor (MUD) transplantation using fludarabine/busulfan (FB) conditioning and in vivo T-cell depletion. For intermediate cytogenetic risk AML transplanted in first complete remission (CR1), multivariate analysis revealed that haplo-TBF significantly increased nonrelapse mortality (NRM) (HR 2.1; p = 0.0006) but did not affect relapse incidence (RI), leukemia-free survival (LFS), overall survival (OS), or graft-versus-host disease-free, relapse-free survival (GRFS). For high cytogenetic risk AML transplanted in CR1, haplo-TBF significantly increased NRM (HR = 2.7; p = 0.02), decreased RI (HR = 0.45; p = 0.03) but had no influence on LFS, OS, or GRFS. For AML transplanted in CR2, haplo-TBF significantly increased NRM (HR = 2.36; p = 0.008), decreased RI (HR = 0.38; p = 0.005), but had no influence on LFS, OS, or GRFS. Finally, for AML patients transplanted with active disease, haplo-TBF had no influence on transplant outcomes. In conclusion, compared to MUD-FB, haplo-TBF increased NRM, reduced RI in high-risk AML in CR, resulting in similar LFS, OS, and GRFS. These results comparing two different approaches support the use of a haploidentical family donor for high-risk AML patients lacking a matched sibling donor.

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.

Acute myeloid leukemia (AML) with FLT3-mutation carries a poor prognosis, and allogeneic stem cell transplantation (allo-SCT) is recommended at first complete remission (CR1). We assessed 462 adults (median age 50 years) with FLT3-mutated AML allografted between 2010 and 2015 from a matched related (40%), unrelated (49%), or haploidentical donor (11%). The median follow-up of alive patients was 39 months. Day-100 acute graft versus host disease (GVHD) grades II-IV and III-IV were encountered in 26% and 9%, whereas the 2-year incidence of chronic and extensive chronic GVHD were 34% and 16%, respectively. The 2-year incidences of relapse and nonrelapse mortality were 34% and 15%, respectively. The 2-year leukemia-free survival, overall survival (OS), and GVHD relapse-free survival (GRFS) were 51%, 59%, and 38%, respectively. In multivariate analysis, NPM1-mutation, transplantation in CR1, in vivo T-cell depletion, and posttransplant sorafenib improved OS, whereas more than one induction (late CR1) negatively affected OS. Similarly, NPM1-mutation, a haploidentical donor, T-cell depletion, and sorafenib maintenance improved GRFS, whereas late CR1 or persistent disease negatively affected it. In conclusion, FLT3-mutated AML remains a challenge even following allo-SCT. In vivo T-cell depletion and posttransplant sorafenib significantly improve OS and GRFS, and may be considered as standard of care. ispartof: Clin Hematol Int vol:1 issue:1 pages:58-74 ispartof: location:United States status: Published online

Donor lymphocyte infusion (DLI) can be proposed to treat or prevent the relapse of malignant hemopathies following allogeneic stem cell transplantation. The efficiency has been mainly reported in the treatment of CML and low-grade lymphomas while the anti-tumoral activity is less in forms of acute leukemia and myelodysplastic syndromes. The GVL benefit should always be compared to the possible toxic effects of GVHD. This article updates the initial SFGM-TC recommendations, proposed in 2013, that were focused on the use of DLI. Doses of DLI in the context of haplo-identical stem cell transplantation are now indicated. We confirm that remaining mobilized stem cells may be used as classical DLI. The definition and the place of preemptive and prophylactic DLI are precisely given. Recommendations regarding the quality of thawed DLI as well as necessary clinical and biological follow-up are also described in detail., Les injections de lymphocytes du donneur (DLI) peuvent être proposées pour traiter ou prévenir la rechute d’une hémopathie maligne après allogreffe de cellules souches hématopoïétiques. L’efficacité est principalement rapportée dans le traitement de la leucémie myéloïde chronique et les lymphomes à caractère indolent. L’activité antitumorale est moindre pour les leucémies aiguës et les syndromes myélodysplasiques. L’effet bénéfique « greffon versus leucémie » (GVL) doit toujours être évalué par rapport à la morbi-mortalité possible liée à la réaction du greffon contre l’hôte (GVHD). Les premières recommandations de la SFGM-TC de 2013 concernant l’utilisation des DLI sont mises à jour. Les doses de DLI dans le cadre des greffes haplo-identiques sont indiquées. L’excédent de cellules souches périphériques mobilisées par rhG-CSF peut être utilisé comme DLI. La définition et la place des DLI préemptives et prophylactiques sont précisées. Des recommandations sont également proposées concernant l’évaluation de la qualité des DLI décongelées et le suivi clinique et biologique après DLI.

International audience; IntroductionThe frequency of invasive fungal diseases (IFDs) has increased in recent years. Within a context where both treatments and guidelines are fast evolving, we aim to shed new light on IFD management in hematologic departments in France.MethodsA multicenter cross-sectional observational study was prospectively conducted in 24 French centers in September and October 2013.ResultsFour hundred ninety-four hospitalized children and adult patients suffering from hematologic malignancy were enrolled: 147 (30%) were allogeneic hematopoietic stem cell transplant (HSCT) recipients, 131 (27%) were patients with acute myeloblastic leukemia or myelodysplastic syndrome (MDS), 71 (14%) were patients with acute lymphoblastic leukemia who did not undergo allogeneic HSCT, and the 145 (29%) remaining patients did not belong to the three above groups. Two hundred forty-six patients (50%) received antifungal treatment, which was prophylactic in 187 (76%) treated patients. These rates were similar across all groups (63–80%). Patients received prophylaxis with an azole (79%), intravenous amphotericin B formulation (10%), echinocandin (9%), or two combination drugs (2%).ConclusionResults indicate that prophylaxis is the leading antifungal strategy in French hematology units, regardless of the disease condition, representing 76% of prescriptions for antifungal therapy.FundingAstellas Pharma France.

Despite major improvements in the treatment of multiple myeloma (MM), the majority of patients will eventually relapse.[1][1] Those patients may benefit most from the potentially curative effect of graft versus myeloma effect of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and its

Evaluation of bone marrow involvement (BMI) is paramount in diffuse large B-cell lymphoma (DLBCL) for prognostic and therapeutic reasons. PET/CT scanner (PET) is now a routine examination for the staging of DLBCL with prognostic and therapeutic implications. This study evaluates the role of PET for detecting marrow involvement compared to bone marrow biopsy (BMB). This monocentric study included 54 patients diagnosed with DLBCL between 2009 and 2013 and who had FDG PET/CT in a pre-treatment setting. A correlation analysis of the detection of BMI by PET and BMB was performed. A prognostic evaluation of BMI by BMB and/or PET/CT and correlation with an overall 2-year survival were analyzed. PET was more sensitive for the detection of BMI than BMB (92.3% vs. 38.5%). It can be considered a discriminatory Pre-BMB test with a negative predictive value of 97.6%. In addition, BMI by PET had a prognostic value with strong correlation with progression-free survival (PFS) (HR = 3.81; p = 0.013) and overall survival (OS) (HR = 4.12; p = 0.03) while the BMB had not. PET shows superior performance to the BMB for the detection of marrow involvement in DLBCL. It may be considered as the first line examination of bone marrow instead of the biopsy.

Several factors affect the outcome of allogeneic stem cell transplantation (Allo-SCT) in hematologic malignancies patients. Proximity to the transplant center could be an independent factor that affects overall survival (OS). This study has been conducted at American University of Beirut Medical Center (AUBMC), a referral center for the Middle East located in Lebanon. Our aim was to determine the differences in the survival between patients residing in Lebanon and those referred from abroad.We identified 161 consecutive adults patients who underwent allo-SCT between January 2007 and December 2016. One hundred and three patients (64%) were residing in Lebanon, and 58 patients (36%) were referred from abroad. Follow up on patients residing in Lebanon was done mainly via regular clinic visits, while those residing outside Lebanon was either by clinic appointment, and/or phone calls in case they could not travel to Lebanon.All patients engrafted. The median time to neutrophil engraftment was 15 days in both groups but with different ranges (10-23) and (9-35) days in local and foreign groups respectively. In Local group 68 (66%) patients were in Complete remission (CR) at transplant, from those 39 (57) were in first CR (CR1), 18 (26) were in second CR (CR2), and 11(16) were third CR (CR3). vs. 35 (34%) were in progression disease/relapsed disease (PR/RD) and Stable disease/partial response(SD/PR) at transplant, in foreign group 34 (59%) patients were at CR at time of transplant, from those 20 (59) were in CR1, 8(23) were in CR2, and 6(18) were in CR3, while 24 (41%) patients were in PR/RD and (SD/PR) at time of transplant. The incidence of acute graft versus host disease (aGVHD) was higher in local group with 30 cases (29%) and 11 cases (19%) in foreign group (P= 0.188). Similarly, the incidence of chronic graft versus host disease (cGVHD) in local group was superior to foreign group, with 23 (22%) patients vs. 11 (19%) patients respectively (P =0.6904). After a median follow up of 16 months (range, 1-99), 59 (57%) and 34 (59%) patients were alive in the local and foreign group respectively. The median OS was 55 months in local groups, but it has not been reached in foreign group. The median progression free survival (PFS) has not been reached in both groups. The cause of death was classified into two categories, disease related and TRM. In the local group, 44 (43%) patients died, from those, 27 (26%) were disease related and 17 (14%) due to TRM. Whereas 24 (41%) patients died in foreign group, from those 12 (21%) deaths were disease related, while 7 (12%) deaths were TRM.Our results imply that the geographical distance has no impact on the OS, however, we have found that it might have impact on the PFS, but we should take into consideration that more patients in local group underwent Haploidentical bone marrow transplant. These findings need to be verified in larger scale studies.

Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin’s lymphoma (NHL) comprising around 7% of adult NHL. It is characterized by a chromosomal translocation t(11:14) and overexpression of Cyclin D1. The incidence of secondary gastrointestinal tract involvement in MCL ranges from 10 to 28% in various series. However primary gastrointestinal MCL is very rare, accounting for only 1 to 4% of primary gastrointestinal lymphomas. The most common endoscopic feature of primary intestinal MCL is multiple lymphomatous polyposis. In rare cases it presents as protruded lesions or superficial lesions. Single colonic mass presentation is an extremely infrequent presentation. MCL has an aggressive course with quick progression, and most cases are discovered in the advanced stages. Colonic biopsies with histologic examination and specific immunohistochemical staining are the gold standard for a proper diagnosis. We report a case of a single mass forming mantle cell lymphoma of the ascending colon in a 57-year-old female patient with unusual colonoscopic and radiologic features and describe the therapy the patient received, thereby adding to the spectrum of clinical presentations of this aggressive lymphoproliferative disorder.

Background. Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 monoclonal antibody conjugated with calicheamicin, used in acute myeloid leukemia (AML) either as monotherapy or in association with chemotherapeutic agents (Hamann et al. Bioconjug. Chem 2002). It is known to induce a significant liver toxicity that might increase the risk of sinusoidal obstruction syndrome (SOS), especially in patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT). Risk is especially high in patients transplanted within a short interval from last GO dose (≤ 3.5 months) (Wadleigh et al. Blood 2003). The current retrospective analysis aimed to assess the incidence of SOS and the outcome of AML patients receiving GO before allo-HSCT. Patients and methods. The primary endpoint of the study was the assessment of SOS incidence in a series of 146 adult patients (71 women and 75 men) with AML undergoing allo-HSCT after prior exposure to GO. Relevant data were captured by a specific designed questionnaire focusing on SOS (Med C) that was distributed to all EBMT centers. Secondary endpoints were engraftment, non-relapse mortality (NRM), graft-versus host disease (GVHD), leukemia-free survival (LFS) and overall survival (OS). Median age was 50 years (range 19-70). In most cases (n=127 out of 137 for which the information was available, 93%) GO was administered in parallel with other chemotherapeutic agents. Median GO dose was 3 mg/m2. Median number of cycles before allo-HSCT was 1 (range 1-6). The majority of the patients (n=79, 54%) received GO as induction treatment, while 51 (35%) and 16 (11%) received GO for relapsing or primary refractory disease, respectively. At time of allo-HSCT 97 (66%) patients were in complete remission. Of note, 11 patients underwent prior allo-HSCT and 8 patients prior auto-HSCT. Most patients received a reduced intensity conditioning (RIC) regimen pre allo-HSCT (n=84, 58%). SOS prophylaxis was given in a total of 69 patients (heparin n=57, ursodeoxycholic acid n=8, and defibrotide n=4). Cumulative incidence (CI) and Kaplan-Meier estimates were used when appropriate; Cox model was used for multivariate analysis. Results. Overall, cumulative incidence of SOS was 7.75% (95% CI 4.1-12.9) (n=11). Among patients receiving RIC, 4 (4,9%) developed SOS as compared to 7 (11,5%) among patients receiving MAC regimen (p=NS). SOS was the main cause of death in 3 out of 11 cases. Median interval between last GO dose and allo-HSCT was 130 days (range 13-1126). Neither OS nor SOS incidence differed significantly for patients receiving GO shortly before allo-HSCT (≤ 3.5 months) as compared to the others. None of the analyzed risk factors had an impact on the risk of SOS in our study. With a median of 15 days, CI of neutrophil and platelet engraftment was 93.8% (95% CI 88.1-96,8) and 89% (95% CI 82.3-93.3), respectively. CI of acute GVHD at day 100 was 30.6% (95% CI 23-38.2), occurring in 84 patients (out of them 45 had grade II-IV GVHD), while CI of chronic GVHD at 5 years was 25.5% (95% CI 18.6-33). With a median follow-up of 64 months the probability of OS and LFS at 5 years was 40% (95% CI: 31-48) and 37% (95% CI: 29-45), respectively. Cumulative RI and NRM at 5 years were 42% (95% CI: 34-50%) and 21% (95% CI: 14-28), respectively. In multivariate analysis patients transplanted with an active disease relapsed more often and had worse LFS and OS, while patients presenting with liver abnormalities before allo-HSCT had a worse OS (p Conclusion. Our results in a large cohort of AML patients show that GO administration prior to allo-HSCT does not result in an excessive incidence of SOS as compared to historical controls reported in the literature (Carreras et al. Biol. Blood Marrow Transplant 2011). Notably incidence is low even when allo-HSCT is performed within a short interval from the last dose of GO. Disclosures Fanin: Novartis Farma: Speakers Bureau. Mohty:Janssen: Honoraria; Celgene: Honoraria. Nagler:Novaratis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding.

International audience; The introduction of reduced intensity/toxicity conditioning regimens has allowed allogeneic hematopoietic cell transplantation to be performed in patients who were previously considered too old or otherwise unfit. Although it led to a reduction in non-relapse mortality, disease control remains a major challenge. We studied the outcome of 165 patients with acute myeloid leukemia (n=124) or myelodysplastic syndrome (n=41) transplanted after conditioning with fludarabine (30 mg/m2/day for 5 days), intravenous busulfan (either 260 mg/m2: reduced intensity conditioning, or 390–520 mg/m2: reduced toxicity conditioning), and rabbit anti-thymoglobulin (2.5 mg/kg/day for 2 days). The median age of the patients at transplantation was 56.8 years. The 2-year relapse incidence was 29% (23% versus 39% for patients transplanted in first complete remission and those transplanted beyond first complete remission, respectively; P=0.008). The 2-year progression-free survival rate was 57% (95% CI: 49.9–65). It was higher in the groups with favorable or intermediate cytogenetics than in the group with unfavorable cytogenetics (72.7%, 60.5%, and 45.7%, respectively; P=0.03). The cumulative incidence of grades 2–4 and 3–4 acute graft-versus-host disease at day 100 was 19.3% and 7.9%, respectively. The cumulative incidence of chronic graft-versus-host disease at 1 year was 21.6% (severe forms: 7.8%). Non-relapse mortality at 1 year reached 11%. The 2-year overall survival rate was 61.8% (95% CI: 54.8–69.7). Unfavorable karyotype and disease status beyond first complete remission were associated with a poorer survival. This well-tolerated conditioning platform can lead to long-term disease control and offers possibilities of modulation according to disease stage or further development.

It has been reported that chronic graft-versus-host disease (cGVHD) is associated with significant morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). The risk of relapse is generally reduced when cGVHD is present, but prognosis may be affected by increased toxicity and/or risk of infection associated with immunosuppressive treatment (IST). We performed a longitudinal data analysis of cGVHD, including the evolution of cGVHD itself over time in response to IST, in a single-center cohort of 313 consecutive patients undergoing allo-SCT. We found that lack of sustained response without withdrawal of IST within 6 months of cGVHD development was associated with higher transplantation-related mortality (hazard ratio, 2.32; 95% confidence interval, 1.24-4.33) compared with cGVHD-free patients. Conversely, response conferred better overall survival (hazard ratio, 0.42; 95% confidence interval, 0.18-0.95). Our analytical approach allowed us to integrate the evolution of cGVHD in a predictive model of transplantation outcome; notably, remission associated with permanent discontinuation of IST within the first 6 months from the occurrence of cGVHD seemed to correlate most closely with final outcome. Further confirmation from larger studies is needed.

JC virus disease is a rare infectious complication after allogeneic hematopoietic stem cell transplantation. There is a few data in the literature on the frequency of JCV after allogeneic umbilical cord blood transplantation (UCBT). We describe a rare occurrence of Progressive multifocal leuko-encephalopathy (PML), with a rapidly fatal outcome, in one patient after UCBT.This case report demonstrates that patients presenting neurological symptoms after UCBT, the JCV encephalitis must be early suspected. These findings could have practical implications in patients presenting neurological symptoms and radiological signs after UCBT. Unfortunately inadequate drug penetration and the multi antiviral resistance as well as the severely immuno-suppressed state of this patient may have contributed to treatment failure.

Purpose To investigate the impact of prior-to-transplantation azacitidine (AZA) on patient outcome after allogeneic stem-cell transplantation (alloSCT) for myelodysplastic syndrome (MDS). Patients and Methods Of the 265 consecutive patients who underwent alloSCT for MDS between October 2005 and December 2009, 163 had received cytoreductive treatment prior to transplantation, including induction chemotherapy (ICT) alone (ICT group; n = 98), AZA alone (AZA group; n = 48), or AZA preceded or followed by ICT (AZA-ICT group; n = 17). At diagnosis, 126 patients (77%) had an excess of marrow blasts, and 95 patients (58%) had intermediate-2 or high-risk MDS according to the International Prognostic Scoring System (IPSS). Progression to more advanced disease before alloSCT was recorded in 67 patients. Donors were sibling (n = 75) or HLA-matched unrelated (10/10; n = 88). They received blood (n = 142) or marrow (n = 21) grafts following either myeloablative (n = 33) or reduced intensity (n = 130) conditioning. Results With a median follow-up of 38.7 months, 3-year outcomes in the AZA, ICT, and AZA-ICT groups were 55%, 48%, and 32% (P = .07) for overall survival (OS); 42%, 44%, and 29% (P = .14) for event-free survival (EFS); 40%, 37%, and 36% (P = .86) for relapse; and 19%, 20%, and 35% (P = .24) for nonrelapse mortality (NRM), respectively. Multivariate analysis confirmed the absence of statistical differences between the AZA and the ICT groups in terms of OS, EFS, relapse, and NRM. Conclusion With the goal of downstaging underlying disease before alloSCT, AZA alone led to outcomes similar to those for standard ICT.

Cytomegalovirus (CMV) infection is a serious complication that may occur in the weeks or months following bone marrow transplantation. However, both Ganciclovir and the CMV infection itself can cause marrow toxicity, notably neutropenia, that may consequently expose these immunosuppressed patients to life-threatening bacterial and/or fungal infections. The aim of this retrospective study was to identify factors associated with the occurrence of grade III–IV neutropenia among patients receiving pre-emptive Ganciclovir therapy after allogeneic stem cell transplantation at our Institution. We identified 547 consecutive patients transplanted from January 2005 to June 2011 at our Institution. In all, 190 patients (35%) presented with CMV reactivation of whom 30 patients (5%) were excluded from the analysis because they already had neutropenia at the time of reactivation. Finally, 160 (29%) patients were analysed. According to multivariate analysis, at the time of treatment initiation, the risk factors significantly associated with a grade III–IV Ganciclovir-related neutropenia included a high viral load (hazard ratio (HR) = 2.68, 95% CI 1.25–5.737, p 0.01); an absolute neutrophil count >3000 was a protective factor (HR = 0.26, 95% CI 0.125–0.545, p 2 mg/dL was associated with higher Ganciclovir-related neutropenia (HR = 2.4, 95% CI 1.11–5.17, p 0.002). This large analysis revealed three risk factors for Ganciclovir-related neutropenia among patients with CMV reactivation after allogeneic stem cell transplantation; prompt identification of patients at risk when antiviral therapy is started may allow clinicians to adopt adequate preventive measures, so reducing the morbidity and mortality associated with CMV reactivation.

Recently, the administration of high-dose cyclophosphamide (Cy) after T cell–replete haploidentical stem cell infusion has been reported to be feasible and effective. In the original study, bone marrow (BM) was used as the source of stem cells. Here, we retrospectively analyzed the use of BM versus peripheral blood stem cells (PBSCs) in a cohort of patients receiving haploidentical T cell–replete transplantation after a nonmyeloablative conditioning regimen with postinfusion Cy. In the PBSC versus BM groups, the incidence of acute graft-versus-host disease (GVHD) was 33% versus 25%, respectively, and the incidence of chronic GVHD was 13% versus 13%, respectively. The median time to achieve a safe and unsupported absolute neutrophil and platelet count was 20 versus 21 days and 27 versus 29 days, respectively. The incidence of engraftment was also similar in the 2 cohorts. The 1-year nonrelapse mortality rate was 12% versus 22%, respectively (P = .96). Finally, nonsignificant differences in survival were observed. In conclusion, the use of PBSCs instead of BM after T cell–replete haploidentical transplantation did not appear to be detrimental in terms of either GVHD or engraftment rate. PBSCs could be a valid alternative to BM after transplantation from a haploidentical donor using postinfusion Cy.

It has recently been shown that a T cell–replete allogeneic (allo) hematopoietic stem cell transplantation (HSCT) from a haploidentical donor (haplo-ID) could be a valid treatment for hematological malignancies. However, little data exist concerning older populations. We provided transplantation to 31 patients over the age of 55 years from a haplo-ID and compared their outcomes with patients of the same ages who underwent transplantation from a matched related (MRD) or an unrelated donor (UD). All 3 groups were comparable, except for their conditioning. Patients in haplo-ID group received 2 days of post-transplantation high-dose cyclophosphamide followed by cyclosporine A and mycophenolate mofetil, whereas patients in other groups received pretransplantation antithymocyte globulin, cyclosporine A, and additional mycophenolate mofetil in case of 1-antigen mismatch. All patients but 1 in the haplo-ID group engrafted. The incidence of grades 2 to 4 acute graft-versus-host disease (GVHD) was not statistically different between recipients from haplo-ID (cumulative incidence, 23%) and MRD (cumulative incidence, 21%) transplantations but it was lower than after UD HSCT (cumulative incidence, 44%). No patient in the haplo-ID group developed severe chronic GVHD, compared with cumulative incidences of 16% and 14% after MRD (P = .02) and UD (P = .03) grafts, respectively. The cumulative incidences of relapse were similar in the 3 groups, whereas nonrelapse mortality after UD HSCT was 3-fold higher than after haplo-ID or MRD HSCT. Overall, 2-year overall survival (70%), progression-free survival (67%), and progression and severe chronic GVHD–free survival (67%) probabilities after haplo-ID did not statistically differ from MRD transplantation (78%, 64%, and 51%, respectively), although they were higher than after UD transplantation (51% [P = .08], 38% [P = .02], and 31% [P = .007]). We conclude that T cell–replete haplo-ID HSCT followed by post-transplantation high-dose- cyclophosphamide in patients over 55 years is associated with promising results, similar to MRD HSCT, and is deserving prospective evaluation.

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is recommended for patients with high-risk acute myeloid leukemia (AML). In many situations, a matched related (MRD) or matched unrelated donor (MUD) is lacking, in which case unrelated cord blood units (UCB) provide an alternative. We analyzed the outcome of consecutive high-risk AML patients prepared with reduced-intensity conditioning (RIC) regimens and allografted with UCB (n = 32) and compared their outcome with high-risk AML patients who underwent transplantation with MRD/MUD (n = 49) in the same period of time. Grade III to IV acute graft-versus-host disease (GVHD) occurred slightly more frequently in the UCB group (25%) than in the MRD/MUD group (8%) (P = .069). Conversely, we found a lower incidence of extensive chronic GVHD in the UCB group (6%) than in the MRD/MUD group (20%, P = .085). Nonrelapse mortality at 4 years was 16% and 22% in the UCB and MRD/MUD groups, respectively (P = .529). The cumulative incidence of relapse at 4 years was significantly higher in the UCB group (60%) than in the MRD/MUD group (27%, P = .006). Leukemia-free survival (LFS) and overall survival (OS) at 4 years were 25% and 34%, respectively, in the UCB group and 50% and 56%, respectively, in the MRD/MUD group (LFS, P = .029; OS, P = .072). Multivariate analyses adjusted by cytogenetics and disease status at the time of Allo-HSCT revealed that use of UCB remained an independent predictive factor of shorter LFS (hazard ratio, 2.0; 95% confidence interval, 1.1 to 3.6; P = .018), and was associated with a trend for shorter OS (hazard ratio, 1.7; 95% confidence interval, .9 to 3.2; P = .093). Whereas UCB provides an alternative for patients with high-risk AML lacking an MRD/MUD, the high incidence of relapse after RIC-based UCB Allo-HSCT is a concern. Attempts to improve leukemic control with UCB Allo-HSCT are warranted, as well as the evaluation of other alternative donors in this context.