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Summary: Pre‐transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo‐HCT). The impact of MRD on the outcomes of post‐transplant cyclophosphamide (PTCy)‐based allo‐HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD−], n = 165; MRD positive [MRD+], n = 107) with a median follow‐up of 19 (range: 16–24) months were studied. The incidence of grades II–IV and grades III–IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2‐year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD− cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39–4.72), lower leukaemia‐free survival (LFS) (HR = 2.04, 95% CI: 1.23–3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04–3.25) and GVHD‐free, relapse‐free survival (GRFS) (HR = 1.69, 95% CI: 1.10–2.58). MRD status did not have a significant impact on non‐relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo‐HCT with PTCy, pre‐transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS. [ABSTRACT FROM AUTHOR]

Background: Both mismatched unrelated donor (MMUD) and haploidentical (haplo) transplantation are valid options in patients with high‐risk acute lymphoblastic leukemia (ALL) lacking a matched donor. Methods: The study compared the outcomes of adult patients with ALL in complete remission (CR) who underwent 9/10 MMUD versus haplo transplantation with posttransplant cyclophosphamide (PTCy) as graft‐vs‐host disease (GVHD) prophylaxis in 2010–2020. Results: The study included 781 patients (MMUD, 103; haplo, 678). The median age was 40 (19–73) and 38 (18–75) years, respectively (p =.51). The most frequent immunosuppression agents added to PTCy were mycophenolate mofetil (MMF)/cyclosporine A and MMF/tacrolimus. In vivo T‐cell depletion (anti‐thymocyte globulin) was administered to 21% and 8% of the transplants, respectively (p <.0001). Neutrophil (absolute neutrophil count >0.5 × 109/L) recovery was achieved in 97.1% versus 96.7% versus (p = 1) in MMUD and haplo, respectively. Nonrelapse mortality and relapse incidence were not significantly different between MMUD and haplo, hazard ratio (HR) = 1.45 (95% confidence interval [CI], 0.81–2.62; p =.21) and HR = 0.81 (95% CI, 0.52–1.28, p =.38), respectively. HRs for leukemia‐free survival, overall survival, and GVHD‐free, relapse‐free survival were respectively, HR = 1.05 (95% CI, 0.73–1.50, p =.8), HR = 1.17 (95% CI, 0.77–1.76, p =.46), and HR = 1.07 (95% CI, 0.78–1.46, p =.7) for haplo compared to MMUD. Acute (a)GVHD grade 2–4 was significantly higher with haplo, HR = 1.73 (95% CI, 1.08–2.76, p =.023), whereas aGVHD grade 3–4 and chronic GVHD did not differ significantly between the two transplant groups. Conclusion: Outcomes of MMUD and haplo transplants with PTCy‐based GVHD prophylaxis for ALL patients in CR are similar, apart from a higher incidence of aGVHD with haplo transplants. The outcomes of mismatch unrelated and haploidentical transplants in patients with acute lymphocytic leukemia (ALL) in complete remission are similar. The donor pool for patients with ALL who are in need of allogeneic transplantation and do not have a human leukocyte antigen‐compatible donor is, therefore, enlarged. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of haploidentical hematopoietic cell transplantation (haplo‐HCT) with posttransplantation cyclophosphamide prophylaxis is gaining traction in patients with acute lymphoblastic leukemia (ALL). METHODS: The Acute Leukemia Working Party/European Society for Blood and Marrow Transplantation registry was used to evaluate the outcomes of adult patients with ALL who underwent haplo‐HCT during 2011 through 2015 and compared them with the outcomes of those who underwent transplantation during 2016 through 2018. RESULTS: The analysis consisted of 195 patients, including 79 who underwent transplantation during 2011 through 2015 and 116 who underwent transplantation during 2016 through 2018. Overall, the 2‐year leukemia‐free survival and relapse incidence rates were 56.5% and 21%, respectively. The 100‐day incidence of grade 2 through 4 acute graft‐vs‐host disease (GVHD) was 34.5%. The rates of nonrelapse mortality (NRM) and overall survival (OS) were 22.5% and 64.7%, respectively. Patients who underwent transplantation during 2016 through 2018 experienced improved rates of leukemia‐free survival (64.9% vs 47.3%; P =.019) and OS (75.5% vs 53.5%; P =.006). Patients who underwent transplantation during 2016 through 2018 developed more grade 2 through 4 acute GVHD (42% vs 26.4%; P =.047). The incidence of relapse, GVHD‐free/relapse‐free survival, grade 3 and 4 acute GVHD, chronic GVHD, and extensive chronic GVHD did not differ significantly between groups. In multivariate analysis, more recently transplanted patients had a significantly reduced risk of NRM (hazard ratio, 0.44; 95% CI, 0.22‐0.89; P =.022) and improved OS (hazard ratio, 0.47; 95% CI, 0.26‐0.86; P =.014). A comparable analysis of patients who had acute myeloid leukemia during the same timeframes did not reveal any statistically significant differences in any outcomes. CONCLUSIONS: The outcome of adult patients with ALL who receive posttransplant cyclophosphamide has improved over time, with an impressive 2‐year OS of 75% and, most recently, an NRM rate of only 17%. In patients with acute lymphocytic leukemia who undergo haploidentical transplantation with posttransplantation cyclophosphamide prophylaxis, significant improvements in leukemia‐free survival and survival are observed in more recently transplanted patients. A nonrelapse mortality rate of 17% is reported in recently transplanted patients with acute lymphocytic leukemia who receive posttransplantation cyclophosphamide prophylaxis. [ABSTRACT FROM AUTHOR]

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]

Background: Relapse and transplant-related complications are leading causes of mortality after hematopoietic stem cell transplantation (HSCT). Suicides and accidents have not been studied in these patients. This study sought to determine whether there is an excess of suicide and accidental deaths after HSCT, and to determine risk factors.Methods: The incidence of suicidal and accidental death in patients after undergoing HSCT, standardized mortality ratio (SMR), and absolute excess risk (AER) of suicide and accidental deaths was determined, compared with the general European population. A case-control analysis was done to define factors associated with suicide and accidental deaths. Data were derived from the European Group for Blood and Marrow Transplantation Registry, including 294,922 patients who underwent autologous or allogeneic HSCT from 1980 to 2009.Results: The 10-year cumulative incidence of suicide and accidental deaths was 101.8 and 55.6 per 100,000 patients, respectively. SMR and AER of suicide after HSCT were 2.12 (P < .001) and 10.91, higher than in the European general population for 100,000 deaths, respectively. SMR and AER of accidental death were 1.23 (P < .05) and 2.54, respectively. In the case-control study, relapses were more frequent among patients who committed suicide after autologous HSCT (37% versus 18%; P < .0001). Chronic graft-versus-host disease was higher among patients who committed suicide after allogeneic HSCT (64% versus 37%; P = .001).Conclusions: There is an excess of deaths due to suicide and accidents in patients after undergoing HSCT as compared with the European general population. Relapse was associated with more suicide and accidental deaths after autologous HSCT, and chronic graft-versus-host disease was associated with more deaths by suicide after allogeneic HSCT. [ABSTRACT FROM AUTHOR]

BACKGROUND Relapse and transplant-related complications are leading causes of mortality after hematopoietic stem cell transplantation (HSCT). Suicides and accidents have not been studied in these patients. This study sought to determine whether there is an excess of suicide and accidental deaths after HSCT, and to determine risk factors. METHODS The incidence of suicidal and accidental death in patients after undergoing HSCT, standardized mortality ratio (SMR), and absolute excess risk (AER) of suicide and accidental deaths was determined, compared with the general European population. A case-control analysis was done to define factors associated with suicide and accidental deaths. Data were derived from the European Group for Blood and Marrow Transplantation Registry, including 294,922 patients who underwent autologous or allogeneic HSCT from 1980 to 2009. RESULTS The 10-year cumulative incidence of suicide and accidental deaths was 101.8 and 55.6 per 100,000 patients, respectively. SMR and AER of suicide after HSCT were 2.12 ( P < .001) and 10.91, higher than in the European general population for 100,000 deaths, respectively. SMR and AER of accidental death were 1.23 ( P < .05) and 2.54, respectively. In the case-control study, relapses were more frequent among patients who committed suicide after autologous HSCT (37% versus 18%; P < .0001). Chronic graft-versus-host disease was higher among patients who committed suicide after allogeneic HSCT (64% versus 37%; P = .001). CONCLUSIONS There is an excess of deaths due to suicide and accidents in patients after undergoing HSCT as compared with the European general population. Relapse was associated with more suicide and accidental deaths after autologous HSCT, and chronic graft-versus-host disease was associated with more deaths by suicide after allogeneic HSCT. Cancer 2013;119:2012-2021. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

The aims of this cohort study were to evaluate the association of malignant lymphoproliferative disorders in patients with chronic viral hepatitis and to compare the results with those in individuals with non-alcoholic fatty liver disease. A total of 3,873 patients with chronic liver disease who were seen consecutively in the Liver Disease Outpatient Clinic between January 2001 and July 2007 were assessed retrospectively. The frequency of malignant lymphoproliferative disorders including non-Hodgkin's lymphoma, Hodgkin's lymphoma, and chronic lymphocytic leukemia in these patients was investigated. Of the total, 1,999 patients had chronic hepatitis B infection (male/female: 1,226/773, mean age: 45.1 ± 13.2 years), 978 had chronic hepatitis C infection (male/female: 437/541, mean age: 53.8 ± 13.7 years), and the remaining 896 had non-alcoholic fatty liver disease (male/female: 450/446, mean age: 50.8 ± 11.2 years). A malignant lymphoproliferative disorder was identified in 13 patients (male/female: 9/4, mean age: 52.8 ± 16.8 years) with chronic viral hepatitis, while no case of malignant lymphoproliferative disorder was identified in individuals with non-alcoholic fatty liver disease ( P = 0.048). Among the patients with malignant lymphoproliferative disorders, seven had chronic hepatitis B infection and six had chronic hepatitis C infection; 11 had non-Hodgkin's lymphoma and two had chronic lymphocytic leukemia. All non-Hodgkin's lymphoma cases were B-cell lymphoma. Based on the data obtained in this investigation, the association with malignant lymphoproliferative disorders in chronic viral hepatitis seems to be high as compared to that occurring in individuals with non-alcoholic fatty liver disease. J. Med. Virol. 83:974-980, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Therapy in refractory chronic idiopathic thrombocytopenic purpura is usually a difficult and expensive procedure, with little benefit to the patient, and the results are typically only short-term improvements. In this case report, we study a patient with refractory chronic idiopathic thrombocytopenic purpura who was initially treated with a first line therapy with only partial and temporary benefit, and in whom none of the experimental therapies tried later on resulted in any long lasting effect. In the case study conducted, among all the second-line experimental treatment modalities, only the proposed new protocol (the Modified Malmö Protocol) resulted in a major response. Our results suggest that, the Modified Malmö Protocol may be a promising second-line treatment option for severely refractory idiopathic thrombocytopenic purpura cases. [ABSTRACT FROM AUTHOR]

Objectives: Data regarding the long-term treatment of ursodeoxycholic acid (UDCA) in individuals of chronic graft-vs.-host disease (cGVHD) of the liver are limited. The aims of this prospective study were to determine whether, (i) UDCA treatment is useful as a long-term treatment for individuals with limited cGVHD of the liver following allogeneic hematopoietic cell transplantation, and (ii) the tolerability of UDCA treatment in such individuals. Methods: Fifteen consecutive patients with de novo isolated cGVHD of the liver were included. All individuals were treated with UDCA at a dose of 13 mg/kg/d for 1 yr. Clinical evaluation and laboratory testing were assessed at 30-d intervals during UDCA therapy and every 30 d after discontinuation of UDCA for a total of 3 months. Results: At the end of the treatment, 60% of patients with cGVHD of the liver had normal liver tests, the remaining 40% of patients demonstrated improvement in their abnormal liver tests (partial responders), whereas none of the patients had worsening of the liver tests. When compared with baseline, there was a significant decrease in the serum aminotransferases, alkaline phosphatase and gamma-glutamyl transpeptidase levels after completion of the UDCA treatment at 12 months (p < 0.01). No significant increase in serum liver enzyme tests was observed at the third month after the completion of therapy. Pruritus in seven of nine patients resolved after UDCA treatment. All patients completed their assigned treatment with no major adverse event. Conclusion: Long-term UDCA therapy appears to be effective, safe and tolerable in individuals with cGVHD presenting with isolated liver involvement. [ABSTRACT FROM AUTHOR]

Compares the effects of several replacement fluids used for therapeutic plasma exchange (TPE) on plasma viscosity profile. Use of plasmapheresis as a alternative treatment for several diseases; Cost of TPE; Correlation between plasma viscosity and fibrinogen level.

RBC transfusions should be based on Hb content of the products instead of units. As high as a 50-percent difference in Hb content can be encountered between two units. In this study, 500 mL of whole blood (WB)-generated RBCs according to their total Hb content was used to decrease the number of units ordered by using a new software called Hemosoft. Fifty-one con- secutive patients were enrolled for the study. The median age and male-to-female ratio were 38 (range, 16-69) and 28:23, respectively. Patients’ diagnoses were 38 acute leukemia, 11 lymphoma, and 2 multiple myeloma. When placing orders for RBCs, clinicians were asked to send the information about patient's actual body weight (ABW) and their actual and target Hb. The total blood volume of the recipient was calculated, and the aim was to find the best RBCs from the inventory to decrease two-unit orders to one unit, or four units to two or one unit, all done using Hemosoft. Posttransfusion Hb was checked 2 hours after transfusion. ABW and the median pretransfusion Hb level were 64 kg (range, 40-100) and 7.3 g per dL (5.6-9.8), respectively. 104 RBC units were ordered for 51 patients. In 49 (96.1%), the order was for two units and in 2 (3.9%) was for three units. Hemosoft successfully found a suitable match in 62.7 percent (32/51) of the orders. Actual number of RBCs transfused was two units (41.25) and one unit (58.8%), respectively. In total, 72 units were transfused with a reduction of 30 percent (72/104) from the original order. The median target Hb level was 9.3 g per dL (range, 7.0-11.3) and overall success rate to achieve it was 96.6 percent (range, 73.8-124.2). There was no impact of inventory size, but the ABW of the recipient was found significant to have a successful match unit (58.8 ± 11.0 kg vs. 75.0 ± 8.4 kg, respectively; p = 0.0001). We clearly demonstrated that the number of RBC transfusions could be minimized by the rational use of the Hb content of the units. Although the total numbers of patients who shall benefit from this approach seems to be limited, it allows us to use high-Hb-content units rationally by using an in-house blood-banking software. [ABSTRACT FROM AUTHOR]

Although graft versus host disease (GVHD) is associated with a myriad of cutaneous signs, nail involvement is rarely mentioned in the literature. This study was conducted at the Department of Dermatology and The Bone Marrow Transplantation Unit of Hematology. All patients were examined clinically for presence of nail abnormalities. Severity of nail involvement was assessed as mild or severe. Of 28 patients diagnosed with chronic cutaneous GVHD, 14 had nail manifestations. Longitudinal ridging was the most frequently observed nail change on both the fingernails and the toenails. Severe nail changes such as ptergyium and onicoatrophy were noted in a few patients. As a result we could not find any relationship between nail changes and clinical severity but there was a relationship between nail changes and duration of disease. Nail manifestations could be responsible for considerable morbidity. [ABSTRACT FROM AUTHOR]

Case 1 A 23-year-old woman was diagnosed with chronic myelogenous leukemia in 1997. In 1999, she underwent allogeneic bone marrow transplantation (BMT) from a human leukocyte antigen (HLA)-matched sibling donor after induction chemotherapy with cyclophosphamide and busulfan. At day 46 after BMT, she was discharged with a medication regimen which included cyclosporine, fluconazole, acyclovir, and trimethoprim/sulfamethoxazole. Five months later she developed clusters of vesicles and pain over the right inframammary and right infrascapular areas corresponding to the T5–T6 dermatomes. Herpes zoster infection was diagnosed clinically and acyclovir therapy (3 × 10 mg/kg/day) was started. All lesions healed within 2 weeks leaving atrophic cicatrices and postinflammatory hyperpigmentation. Eight months after BMT, she presented with erythematous and hyperpigmented macules on the malar areas. Follicular hyperkeratosis on the chest and interscapular area, reticulated white plaques on the buccal mucosa, and significant xerosis were also observed on dermatologic examination. Dermatopathologic examination of a biopsy specimen obtained from the lesions on the face was evaluated to be consistent with “atrophic folliculocentric lichen planus.” Two weeks later she was admitted again for new lesions on the trunk. Flat, violaceous, slightly scaly papules were located exactly on the dermatomes of the previous herpes zoster infection (Fig. 1). A biopsy specimen of these lesions showed a dense, subepidermal, band-like, lymphocytic inflammatory infiltrate, vacuolar degeneration of the basal cell layer, and scattered dyskeratotic cells in the epidermis, confirming the diagnosis of lichenoid graft-versus-host disease (GVHD) (Fig. 2a and 2b). Case 2 A 47-year-old woman was diagnosed with chronic myelogenous leukemia in 1998. She underwent allogeneic BMT from an HLA-matched sibling donor after a preoperative chemotherapy regimen with cyclophosphamide and busulfan... [ABSTRACT FROM AUTHOR]

Aregeneratoric anemia (AA) occurs rarely after ABO-incompatible allogeneic peripheral blood stem cell transplantation (alloPBSCT), and its management is generally difficult. Here, we present a 31-year-old white man with myelodysplastic syndrome who developed AA after receiving stem cells from his human leukocyte antigen (HLA) identical, but ABO-incompatible sibling. Because his anti-A antibody titers were high, therapy with conventional doses of erythropoietin and prednisolone failed to treat the AA. Following 8 cycles of plasma exchange and higher doses of erythropoetin and prednisolone as well as danazol administration, anti-A titers decreased, and his anemia improved significantly. In conclusion, to treat and obtain a low titer of antibodies in a patient with AA following an ABO-incompatible alloPBSCT, higher doses of erythopoietin and corticosteroids associated with plasma exchange have to be used. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the correlation of preleukapheresis circulating CD34+ cells/μL, white blood cells (WBC), and platelet counts on the first day of apheresis with the yield of collected CD34+ cell counts in 40 patients with hematological malignancies (n = 29) and solid tumors (n = 11). The median numbers of apheresis cycles, numbers of CD34+ cells, peripheral blood (PB) mononuclear cells, and total nucleated cells collected were 2 (range, 1–4), 5.5 × 106 /kg (range, 0.05–33.78), 2.59 × 108 /kg (range, 0.04–20.68), and 7.36 × 108 /kg (range, 0.15–28.08), respectively. There was a strong correlation between the number of preleukapheresis circulating CD34+ cells/μL and the yield of collected CD34+ cells per kilogram (r = 0.962, p < 0.001). The threshold levels of PB CD34+ cell/μL to obtain ≥1 × 106 /kg and ≥2.5 × 106 /kg CD34+ cell in one collection were 12/μL and 34/μL, respectively. Fifteen of 17 (88%) patients who had ≥34 CD34+ cells/μL in the PB before collection reached the level of ≥2.5 × 106 /kg in a single apheresis. Despite a low r value, WBC and platelet counts on the first day of apheresis also correlated with the yield of collected daily CD34+ cells per kilogram (r = 0.482, p < 0.01 and r = 0.496 p < 0.01, respectively). These data suggest that preleukapheresis circulating CD34+ cells/μL correlated significantly better with the yield of collected CD34+ cells than WBC and platelet counts on the first day of apheresis. Using a value of 34/μL preleukapheresis circulating CD34+ cells as a guide for the timing of peripheral blood stem cells collections can be time saving and cost-effective. [ABSTRACT FROM AUTHOR]