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Donor selection may contribute to improve clinical outcomes of T cell-replete haploidentical stem cell transplantation (Haplo-SCT) with post-transplant cyclophosphamide (PT-Cy). Impact of second-degree related donor (SRD) was not fully elucidated in this platform. We retrospectively compared the outcome of patients receiving Haplo-SCT either from a SRD (n = 31) or a first-degree related donor (FRD, n = 957). Median time to neutrophil and platelet recovery did not differ between a SRD and a FRD transplant (p = 0.599 and 0.587). Cumulative incidence of grade II-IV acute graft-versus host disease (GVHD) and moderate-severe chronic GVHD was 13% and 19% after SRD vs 24% (p = 0.126) and 13% (p = 0.395) after FRD transplant. One-year cumulative incidence of non-relapse mortality (NRM) was 19% for SRD and 20% for FRD (p = 0.435) cohort. The 3-year probability of overall survival (OS) and progression-free survival (PFS) was 42% vs 55% (p = 0.273) and 49% vs 35% (p = 0.280) after SRD and FRD transplant, respectively. After propensity score adjustment or matched pair analysis, the outcome of patients receiving Haplo-SCT from a SRD or a FRD did not differ in terms of NRM, OS, PFS, acute and chronic GVHD. Our results suggest that a SRD is a viable option for Haplo-SCT with PT-Cy when a FRD is not available.

The impact of GVHD and graft-versus-leukemia effect in unrelated cord blood transplantation (UCBT) is controversial. In the Eurocord/ALWP EBMT and JSTCT/JDCHCT collaborative study, we evaluated the impact of GVHD on UCBT outcomes in Japanese and European registries. A total of 3, 690 adult patients with acute leukemia who received their first single UCBT were included. A multivariate analysis of overall survival (OS) revealed a positive impact of grade II acute GVHD compared with grade 0-I GVHD, in the Japanese cohort (hazard ratio (HR), 0.81; P = 0.001), and an adverse impact in the European cohort (HR, 1.37; P = 0.007). A negative impact of grade III-IV acute GVHD on OS was observed regardless of registries. In the analysis of relapse, a positive impact of grade II acutes GVHD compared with grade 0–I GVHD was observed only in the Japanese cohort, regardless of disease risk. The positive impact of limited chronic GVHD on OS was observed only in the Japanese cohort. In conclusion, a positive impact of mild GVHD after a single UCBT was observed only in the Japanese cohort. This could explain the ethnic difference in UCBT outcomes and might contribute to the preference usage of UCBT in Japan., 急性白血病治療における臍帯血移植後の合併症が及ぼす予後への影響 --国際共同研究から明らかになった日欧での違い--. 京都大学プレスリリース. 2021-10-19.

To ensure that observed differences in the scores of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) reflect actual differences in health-related quality of life (HRQoL) rather than measurement bias, measurement invariance needs to be established. We investigated the assumption of measurement invariance of the EORTC QLQ-C30 in patients with hematological malignancies across age, sex, comorbidity, disease type, and time. We used a large database of patients with hematological malignancies, which included HRQoL data collected with the EORTC QLQ-C30. We used the structural equation modeling approach to test for measurement (metric and scalar) invariance across groups (age, sex, comorbidity, disease) and time (baseline, 1 month and 2 month follow-up). Longitudinal invariance was examined in a subgroup of patients diagnosed with myelodysplastic syndromes. Confirmatory factor analyses demonstrated full measurement invariance for age and comorbidity and over time, while support for partial scalar invariance was obtained for sex and disease. Violations of invariance for sex were observed for items of the physical functioning scale and the emotional functioning scale, while for disease type, violations of invariance were observed for items of the physical functioning scale, emotional functioning scale, and the cognitive functioning scale. Our findings support measurement invariance of the EORTC QLQ-C30 in a large sample of patients with hematological malignancies. The results showed that the number of non-invariant items was negligible, suggesting that this questionnaire is a valid and robust measurement tool in patients with hematological malignancies, also for comparisons across groups and time.

This is an update on acute and chronic graft-versus-host disease (GvHD) in 425 patients with hematologic malignancies, undergoing an unmanipulated haploidentical (HAPLO) graft from related donors, with a modified post-transplant cyclophosphamide (PT-CY) regimen. All patients received a myeloablative conditioning regimen, either based on thiotepa busulfan fludarabine (TBF), or on full-dose total body irradiation (TBI). The cumulative incidence of acute GvHD-grade II-IV was 29%, and the CI of GvHD-grade III-IV was 4%. We found older donors and older patients to have higher rates of grade II-IV acute GvHD; female donors, diagnosis, disease phase, year of transplant, and the conditioning regimen had no predictive effect on acute GvHD. There was no impact of grade II GvHD, but a significant impact of grade III-IV acute GvHD, on overall survival. The CI of moderate-severe chronic GvHD was 18%: the major predictor was a previous acute GvHD, followed by combined donor and recipients age. In conclusion, PT-CY given on days+3 + 5 results in a relatively low, but not insignificant risk of acute and chronic GvHD, in patients grafted from the related HAPLO donors. The use of young donors appears to reduce this risk.

Hepatitis B virus (HBV) reactivation during immunosuppressive therapy is common in patients with hematological malignancies, even in case of resolved infection. Prophylaxis of HBV reactivation is universally recommended in stem cell transplant (SCT) recipients and patients treated with anti-CD20 agents (i.e., rituximab). Despite its well-established favorable safety profile, lamivudine (LAM) use in prophylaxis has been debated because of the possible emergence of resistant viral strains. The aim of this study was to investigate the efficacy of LAM in preventing HBV reactivation in allogeneic SCT recipients with a resolved HBV infection. Patients who received first allogeneic SCT in years 2009–2016 were evaluated. Sixty-three patients with resolved infection received LAM prophylaxis and were included in the study. Baseline and post-SCT characteristics were recorded, including rituximab exposure, length of LAM prophylaxis, and time from transplant to the last clinical and virological follow-up. Overall, 39 patients (62%) were male, 39 (62%) had acute myeloid leukemia, 38 (60%) received transplant from haploidentical donor, 29 (53%) received myeloablative conditioning, and 15 (24%) received rituximab post-transplant. Median clinical follow-up was 24 months after SCT (range 0.3–97); median virological follow-up 16 months (range 0.3–78), and median length of LAM prophylaxis of 14.5 months (range 0.3–78). No patient experienced HBV reactivation while on LAM prophylaxis. One patient experienced reactivation 8 months after discontinuing prophylaxis. In this high-risk population, LAM prophylaxis was effective in preventing HBV reactivation in patients with resolved infection. It should be considered a reasonable first-line prophylactic agent to be administered in this setting.

We studied 97 patients who developed cytomegalovirus (CMV) viremia following an allogeneic hemopoietic stem cell transplant (HSCT) between 2010 and 2015, treated with foscarnet, with the aim of assessing efficacy and safety. The donor was unrelated in 30 patients (UD) and a family HLA-haploidentical donor (HAPLO) in 67 patients: the former (UD) received a prophylaxis for graft-versus-host disease (GvHD), based on antithymocyte globulin (ATG); the latter (HAPLO) received GvHD prophylaxis, based on post-transplant cyclophosphamide (PT-CY). Renal and hematological toxicity were defined according to NCI-CTCAE4 criteria. In univariate analysis, CMV response was 84% in HAPLO vs 59% in UD grafts (p = 0.01) and 90 vs 66% (p = 0.02) for patients with a CMV viral load within or over the median value. In multivariate analysis, the CMV viral load was the strongest predictor of response to foscarnet (p = 0.02), followed by donor type (p = 0.06). Renal impairment developed in 14% of the patients. Overall survival was 69%:, advanced phase at transplant (p = 0.01) and ATG-based regimens (p = 0.02), were the only two predicting factor. In conclusion, CMV response to foscarnet treatment is predicted by a lower CMV load and GvHD prophylaxis. Renal toxicity of foscarnet is not a limiting factor.

The primary objective of this study was to investigate whether the presence of comorbidities was associated with a lower health-related quality of life (HRQOL) in elderly patients with chronic myeloid leukemia (CML). A sample of 174 CML patients aged 60 years or above was analyzed. HRQOL was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). A number of pre-selected sociodemographic and disease-related factors were considered as potential confounding factors for the association between comorbidity and HRQOL. Mean age of the 174 patients analyzed was 70 years (range 60–87 years) and 55 % were male. Overall, 111 patients (64 %) reported at least one comorbidity. Analysis stratified by age group category showed a greater proportion of patients with comorbidities in the older sub-group population (≥70 years) compared to younger patients (60 to 69 years). Differences in HRQOL outcomes between patients with no comorbidity at all and those with two or more comorbid conditions were at least twice the magnitude of a clinically meaningful difference in all the physical and mental health scales of the SF-36. In multivariate analysis, after adjusting for key confounding factors, the following scales were significantly lower in those with comorbidity: general health (p

Patients undergoing bone marrow transplantation are profoundly immunosuppressed as a result of their intensive myeloablative chemotherapy and are at high risk for opportunistic fungal infections mainly caused by Candida spp and Aspergillus spp. Trichosporon beigelii (T beigelii) has emerged as a life-threatening opportunistic pathogen in granulocytopenic and immunocompromised hosts and there is a marked increase in cases reported in the literature. Response to antifungal agents is poor, mortality is high and immunological recovery is the most important factor for a favorable outcome in patients with trichosporonosis. We present three cases of T. beigelii infection in patients undergoing allogeneic bone marrow transplantation in our center and we review cases described in the literature.

Early trials of allogeneic bone marrow transplantation (BMT) for homozygous beta-thalassemia and the analyses of results of transplantation in patients less then 16 years old have allowed us to identify three classes of risk using the criteria of degree of hepatomegaly, the degree of portal fibrosis and the quality of the chelation treatment given before the transplant. Patients for whom all three criteria were adverse constituted class 3, patients with none of the adverse criteria constituted class one and patients with one or various association of the adverse criteria formed Class 2. Most patients older than 16 years have disease characteristics that place them in class 3 with very few in class 2. For all the patients with an HLA identical donor we are actually using two Protocols for BMT to whom the patients are assigned on the base of the class they belong to at the time of BMT and independently on the age of the patient. For class 1, class 2 and for class 3 the probabilities of survival and of event-free-survival are respectively of 98% and 94%, 87% and 84%, 100% and 67%. For those patients that were older than 16 years at the time of the transplant, the probabilities of survival are 82% and the probabilities of event-free survival are 79%. Bone marrow transplantation is a new form of radical treatment of thalassemia in those patients with an HLA identical donor.

A case of Kaposi's sarcoma (KS) in an allogenic BMT recipient is reported. A 26-year-old man underwent allogeneic bone marrow transplantation for microdrepanocytosis. He received prolonged immunosuppressive therapy for mild chronic GVHD. Two years after BMT he developed KS localized to the skin. The KS improved rapidly and outcome was complete remission after cessation of immunosuppression.

A 38-year-old man presented on January 2007 with dyspnea on exertion, cough, hepatosplenomegaly, and fever. WHO performance status was 2. White blood cells at admission were 38 9 10/L (neutrophils 35.6 9 10/L). Lactate dehydrogenase was 1513 U/L (ULN 500 U/L); aspartate transaminase and alanine aminotransferase 308 and 360 U/L, respectively (ULN 45 and 55 U/L). Grade 2 (no bleeding, according to CTCAEv3) disseminated intravascular coagulation (DIC) was recorded. Chest X-ray was normal, no ascites was found, and oxygen saturation was 95%. A blast population representing 99% of bone marrow nucleated hematopoietic cells and 90% of the peripheral blood cells was identified. The blasts had typically bilobed or reniform nuclei with inconspicuous cytoplasmic granules and rare Auer rods (Fig. 1). Cytochemistry showed intense reactivity with myeloperoxidase while a nonspecific esterase stain was negative. Immunophenotyping performed on peripheral blood cells showed positivity for CD2 (51%), CD34 (86%), CD38 (80%), CD64 (85%), CD13 (94%), CD45 (99%), HLA DR (35.4%), CD33 (96%), and CD117 (93.5%); CD 56 was not evaluated. CD64 expression displayed a light scatter pattern indistinguishable from that of AML with monocytic differentiation; however, coexpression of CD14 was not detected. Standard cytogenetics analysis showed a t(15;17), confirmed by FISH. At diagnosis, RT-PCR analysis for bcr3 PML/RARa was positive only in the bone marrow specimen (we assumed this was due to poor RNA stability in peripheral blood or a failure in performing the technique). An induction regimen was started immediately, according to the current guidelines [1]: retinoic acid (ATRA) 45 mg/ m/day for 30 days plus four doses of idarubicin 12 mg/m. However, only one idarubicin dose was administered because the patient was deteriorating quickly; moreover, the patient could take only 40 mg of retinoic acid during the third day. In fact, on day ?3, a rapid clinical worsening with fever, abdominal pain, and serious dyspnoea was recorded. A computerized tomography scan revealed massive hepatosplenomegaly, peritoneal, and pleural effusion, and thoracic adenomegaly. The white blood cell count increased to 93 9 10/L; worsening DIC and hepatic and renal failure (LDH 9650 U/L, transaminases 1452 and 1388 U/L and creatinine 2.3 mg/dl) were demonstrated. The patient died due to multi-organ failure on day ?4. Post-mortem examination revealed massive leukemic involvement of the lungs, heart, kidneys, gut, bone marrow, spleen, liver, and brain (Fig. 2). Positivity for bcr3 transcript was confirmed in the bone marrow post-mortem specimen. The microgranular variant (M3v) of acute promyelocytic leukemia (APL) accounts for approximately 20% of all cases [2] and the immunophenotype form is more heterogeneous than classic, with variable expression of CD2, CD34, and HLA DR [3]. It could be a differentiation syndrome developed before treatment, as the CD64 expression might suggest [4], even if the involvement of the heart appears somewhat unusual. However, our interpretation is rather different. We believe that this M3v APL was characterized by some adverse prognostic factors (CD2, bcr3) [4, 5] and an unusual immunophenotype with CD38, CD34, and CD64 expression. A monocytic AML-like course could be hypothesized because of the light scatter pattern of CD64 expression and the aggressive and diffuse extramedullary C. Romani (&) R. Murru M. Pettinau A. A. Di Tucci F. Culurgioni D. Pulisci E. Angelucci Hematology and Transplant Centre, ‘‘Armando Businco’’ Cancer Centre, Cagliari, Italy e-mail: claromani@tiscali.it