Diagnostic clues in a stem cell transplant patient manifested with chronic central nervous system GVHD and IRIS.

Transplant physicians should be aware of the immune deviation-related clinical conditions as allogeneic hematopoietic stem cell transplantation is widely used for the treatment of patients with malignant and non-malignant disorders. Neurological manifestations and graft-versus-host disease (GVHD) may commonly develop in transplant recipients. However, overlapping clinical immunological conditions may lead to diagnostic challenges. Herein, we discussed the differential diagnosis of a patient with immune reconstitution inflammatory syndrome (IRIS) developing on the basis of chronic GVHD.

Assessment of Stem Cell Transplant Eligibility in Recipients with Oral Foci of Infection: Appropriate Conditioning Regimens.

OBJECTIVES: It is unclear whether patients with oral foci of infection should be approved for hematopoietic stem cell transplant with or without posttransplant cyclophosphamide. We compared the presence of oral foci of infection status on the effects of various conditioning regimens for such patients. MATERIALS AND METHODS: Three groups were classified as autologous (carmustine-etoposide-cytarabinemelphalan, mitoxantrone-melphalan, and melphalan 200 mg/m² groups; n = 502 patients), and 6 groups were classified as allogeneic (busulfan-fludarabinerabbit anti-T-lymphocyte globulin, busulfanfludarabine-posttransplant cyclophosphamide, fludarabine-cyclophosphamide-anti-T-lymphocyte globulin, busulfan-fludarabine-anti-T-lymphocyte globulin-posttransplant cyclophosphamide, total body irradiation-posttransplant cyclophosphamide, and other; n = 428 patients). Data were collected from a database that met international accreditation requirements. We evaluated dental radiological findings and calculated interobserver reliability. RESULTS: Oral foci of infections increased febrile neutropenia and bacterial infection frequencies in both groups but only increased mucositis frequency in patients with allogeneic treatment. The frequencies of oral foci of infection-related complications were similar in both the autologous and allogeneic groups. Rate of graft-versus-host disease was not affected by oral foci of infection status. Periodontitis/cysts and periapical lesions increased the risk of infections at day 100 in the mitoxantrone-melphalan group versus the melphalan 200 mg/m² group. We observed no differences among the autologous transplant groups in terms of early mortality. Similarly, no differences in early mortality were observed among the allogeneic groups. CONCLUSIONS: Transplant is a valid option in patients with oral foci of infections undergoing various autologous and allogeneic transplant protocols when time is of the essence, even at myeloablative dose intensities.

Effect of COVID-19 Pandemic on Hematopoietic Stem Cell Transplant Activity: Experience of a JACIE-Accredited Center.

OBJECTIVES: The adoption of international quality and accreditation standards is important for the success of transplant centers. Guidelines from the Joint Accreditation Committee ISCT-Europe and EBMT (JACIE) have enabled quality management of the operations of clinical units of cellular therapy centers, including cell collection and processing, thus minimizing errors and adverse events. COVID-19 has had significant implications for immunocompromised patients, particularly hematopoietic stem cell transplant recipients, as well as their donors and caregivers. Here, we retrospectively examined measures, taken in our transplant center in Turkey during the pandemic period between March 2020 and October 2021, to investigate how JACIE accreditation has affected patient, donor, product, and employee safety. MATERIALS AND METHODS: We analyzed data on transplant activity, as well as donor, patient, product, and employee safety, during the pandemic in 3 separate 6- month periods. The measures were analyzed starting from March 2020, when the first COVID-19 case was seen in Turkey. RESULTS: Since the beginning of the pandemic, 140 patients have undergone stem cell transplant in our center. Stem cell transplant was delayed in 22 patients because of the pandemic. Transplant was also postponed due to COVID-19 positivity in 6 patients, and 2 patients died due to COVID-19 infection during the transplant process. Unrelated donor activity continued to be performed safely throughout this period. COVID- 19 infection developed in 12 of the 52 personnel working in the bone marrow transplant unit, one of whom needed intensive care due to severe pneumonia. In terms of quality management activities, the impact of the pandemic was greatest during the first month. CONCLUSIONS: Results from our retrospective study examining the impact of JACIE accreditation in a stem cell transplant center during the COVID-19 pandemic showed that, when national and international guidelines are followed, JACIE accreditation can facilitate adaptation to changing conditions in transplant centers.

Gonadal Status and Sexual Function at Long-Term Follow-up after Allogeneic Stem Cell Transplantation in Adult Patients with Sickle Cell Disease.

OBJECTIVES: Patients with adult sickle cell disease and severe sequelae are treated with nonmyeloablative allogeneic hematopoietic stem cell transplant. So far, data on gonadal effects are lacking for older cured patients. We assessed the gonadal reserve and sexual function of patients cured of sickle cell disease with transplant and with anti-T-lymphocyte globulin and posttransplant cyclophosphamide-containing regimen within the context of the Baskent Organ Damage Mitigation and Medical Care Development Program. MATERIALS AND METHODS: All adult patients (≥18 years) with sickle cell disease who underwent peripheral stem cell transplant from September 2013 to July 2019 and were graft-versus-host disease free for 2 years and not immunosuppressed were invited to participate in this prospective observational study. Of 61 eligible patients, 43 participants (~10% from international registries) were included (median age at transplant was 29 years; range, 18-45 years). Gonadal status, risk of gonadal damage posttransplant, conception, and sexual function posttransplant were evaluated. RESULTS: Allogeneic hematopoietic stem cell transplant was associated with increased risk of secondary amenorrhea (odds ratio of 93; 95% CI, 4.94-17.50; P = .002) and ovarian insufficiency (odds ratio of 37.8; 95% CI, 2.03 to -700.94; P = .014) but not with female sexual dysfunction. Secondary ovarian insufficiency developed in all women posttransplant. Transplant was associated with significant risk of azoospermia (odds ratio of 4.35; 95% CI, 1.02-18.45; P = .017). Moderate-to-severe erectile dysfunction developed in 2 men (10%). Among female participants, 1 had spontaneous conception that ended in miscarriage and 1 had term delivery after in vitro fertilization. Among male participants, 1 had a child by in vitro fertilization and 1 experienced spontaneous conception. CONCLUSIONS: Although spontaneous conception was shown in our patient group, gonadal damage was evident at >2 years posttransplant. This risk was associated with age in female patients. Better fertility preservation measures should be incorporated into medical care development programs.

Rational use of chronic graft-versus-host treatment alternatives: A systematic review.

Chronic graft versus host disease (cGVHD) is an important transplant complication that affects the quality of life of the recipient by causing organ damage after hematopoietic stem cell transplantation. Prospective controlled studies conducted to date for the treatment of the disease are limited. The results obtained in current studies are not sufficient to establish a standard treatment algorithm. Therefore, clinical experience and adequate clinical observations of the transplant team come to the fore for the treatment strategy to be established. Rational use of available instruments is possible, provided that we understand the mechanisms of the disease and use validated diagnostic and response criteria. In this study, we tried to create a practical workflow by evaluating current literature data.

Is It Possible to be a Stem Cell Donor for the Second Time: A Single-Center Report of 12 Consecutive Procedures.

OBJECTIVES: The use of unrelated donors as a source of stem cells for patients with blood disorders continues to increase. Approximately 5% to 7% of unrelated stem cell donors are asked to donate stem cells a subsequent time to the same or a different patient. We investigated donors who accepted to be a donor for the second time between 2015 and 2021; donors were evaluated in terms of procedure-related complications, product quality, and donor follow-up in a JACIEaccredited (Joint Accreditation Committee of the International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation). MATERIALS AND METHODS: Stem cell collections were performed in accordance with relevant standard operating procedures from healthy volunteer donors. Data on sequence of peripheral blood stem cell, bone marrow, and donor lymphocyte collection procedures; presence of complications during procedures; time between 2 donations; need for granulocyte colonystimulating factor again; and first and second donation types were noted. Data on donor and stem cell products were determined using the hospital information management system. RESULTS: Our study included 12 donors (9 men and 3 women) who donated a second time within the specified date range. In the evaluation of the second donation types, 7 were lymphocyte collection donations, 4 were peripheral blood stem cell donations, and 1 was a bone marrow stem cell donation. In shortterm and long-term follow-ups, there were no complications among the donors. In the second donations, targeted product values were reached. CONCLUSIONS: Although it is safe to have a second donation from a donor for the same patient, collection centers may collect more products than requested from eligible donors.

A Rare and Successfully Managed Complication of Stem Cell Transplantation in an Adult Patient With Sickle Cell Disease: Bone Marrow Necrosis.

Sickle cell disease is the most common genetic disorder in the Eastern Mediterranean region where our transplant center is located. Today, adult patients with sickle cell disease can also be successfully treated with allogeneic hematopoietic stem cell transplantation. Bone marrow necrosis is a rare and serious clinical condition. Herein, we present this complication for the first time in the literature, which developed in the course of allogeneic hematopoietic stem cell transplantation and was successfully managed with additional bone marrow support. The recognition, prevention, and management of this rare and potentially fatal complication, bone marrow necrosis, are vitally important, especially in regions with high prevalence of sickle cell disease.

Comparison of the clinical course of COVID-19 infection in sickle cell disease patients with healthcare professionals.

It is highly expected that COVID-19 infection will have devastating consequences in sickle cell disease (SCD) patients due to endothelial activation and decreased tissue and organ reserve as a result of microvascular ischemia and continuous inflammation. In this study, we aimed to compare the clinical course of COVID-19 in adult SCD patients under the organ injury mitigation and clinical care improvement program (BASCARE) with healthcare professionals without significant comorbid conditions. The study was planned as a retrospective, multicenter and cross-sectional study. Thirty-nine SCD patients, ages 18 to 64 years, and 121 healthcare professionals, ages 21 to 53, were included in the study. The data were collected from the Electronic Health Recording System of PRANA, where SCD patients under the BASCARE program had been registered. The data of other patients were collected from the Electronic Hospital Data Recording System and patient files. In the SCD group, the crude incidence of COVID-19 was 9%, while in healthcare professionals at the same period was 23%. Among the symptoms, besides fever, loss of smell and taste were more prominent in the SCD group than in healthcare professionals. There was a significant difference between the two groups in terms of development of pneumonia, hospitalization, and need for intubation (43 vs 5%, P < 0.00001; 26 vs 7%, P = 0.002; and 10 vs 1%, P = 0.002, respectively). Prophylactic low molecular weight heparin and salicylate were used more in the SCD group than in healthcare professionals group (41 vs 9% and 28 vs 1%; P < 0.0001 for both). The 3-month mortality rate was demonstrated as 5% in the SCD group, while 0 in the healthcare professionals group. One patient in the SCD group became continously dependent on respiratory support. The cause of death was acute chest syndrome in the first case, hepatic necrosis and multi-organ failure in the second case. In conclusion, these observations supported the expectation that the course of COVID-19 in SCD patients will get worse. The BASCARE program applied in SCD patients could not change the poor outcome.

Comparison of Outcomes of Transplant and Nontransplant High-Risk Chronic Lymphocytic Leukemia Patients in the Novel Targeted Therapy Era.

OBJECTIVES: Our aim was to compare patients with high-risk chronic lymphocytic leukemia referred to our transplant center who underwent allogeneic stem cell transplant with those who did not receive this treatment. Factors compared included demographics, clinical characteristics, and survival rates in the novel targeted therapy era. MATERIALS AND METHODS: All 33 patients with high-risk chronic lymphocytic leukemia who were referred to the hematopoietic stem cell transplant center were enrolled in this retrospective, single-center nonrandomized study. Outcomes of patients who received allogeneic stem cell transplant were compared with those of nontransplant patients. Chemoimmunotherapy and ibrutinib were given when indicated. Factors related to overall and progression-free survival were assessed. RESULTS: Thirteen patients underwent allotransplant, and transplant was not done in 20 patients for various reasons. Demographic and clinical features of the transplant and nontransplant groups were similar. The estimated cumulative overall survival was 72.6 ± 15 and 84.3 ± 13 months in the nontransplant and transplant groups, respectively. The 5-year overall and progression-free survival rates in the transplant and nontransplant groups were 57.3%/36.0% and 40%/20.6%, respectively. In the nontransplant group, overall survival of those who used ibrutinib was longer than overall survival in patients in the transplant group who used the same drug, but the difference was not statistically significant. Although not significant, overall survival in patients who did not use ibrutinib was longer in the transplant group than in the nontransplant group. Cox regression analyses showed that transplant, relapse, and Binet stage were independent predictors of overall survival. CONCLUSIONS: In patients who do not use ibrutinib, allogeneic stem cell transplant improved survival compared with nontransplant patients. Addition of ibrutinib provided comparable life expectancies, showing that allogeneic stem cell transplant and ibrutinib may have complementary roles. Transplant is still an independent predictor of overall survival.

Factors Associated With Overall Survival in Acute Myeloid Leukemia Patients Before and After Hematopoietic Stem Cell Transplant.

OBJECTIVES: Our aim was to identify factors associated with overall survival and the efficacy of postrelapse treatment protocols and to determine whether pretransplant consolidation therapy and minimal residual disease status pose a survival benefit. MATERIALS AND METHODS: Patients with acute myeloid leukemia who underwent stem cell transplant between 2007 and 2018 were enrolled retrospectively. The effects of pretransplant cytogenetic and minimal residual disease status, pretransplant consolidation therapies, development of graft-versus-host disease, postrelapse treatment protocols, and type of con-ditioning regimens on overall survival were analyzed. RESULTS: In 76 study patients, the cumulative overall 1- and 5-year relapse probabilities were 67.8% and 58.7%, respectively. Overall survival rates at 3 and 5 years in patients with and without relapse were 23.5% and 0% and 95.9% and 91.1% (P < .001), respectively. Although mean postrelapse overall survival was better with intensive salvage plus donor lymphocyte infusion, no significant differences were shown versus other therapies (intensive salvage, nonintensive salvage, intensive salvage or nonintensive salvage plus donor lymphocyte infusion, or supportive therapy). Twenty-three patients (30.3%) died during the study period with a median survival of 9.6 months. Patients with favorable, intermediate, and unfavorable cytogenetic status showed overall survival of 46.6 ± 10.4, 54.6 ± 4.4, and 36.9 ± 5.9 months (P = .807). Patients with and without minimal residual disease and patients who received or did not receive consolidation therapy had similar overall survival. Relapse was an independent predictor of overall survival (increased mortality risk of 26.22). Patients who developed graft-versus-host disease showed decreased relapse. CONCLUSIONS: Relapse is the most important predictor of overall survival and is associated with poor prognosis. Pretransplant minimal residual status and cytogenetic status showed no effect on relapse rates and overall survival, and consolidation therapy did not improve outcomes.

Role of prophylactic and therapeutic red blood cell exchange in pregnancy with sickle cell disease: Maternal and perinatal outcomes.

BACKGROUND AND AIM: The incidence of fetomaternal complications during pregnancy is high for women with sickle cell disease (SCD), which is the most common hematologic genetic disorder worldwide. Prophylactic red blood cell exchange (pRBCX) has been shown to be efficient, safe, and feasible for preventing complications. The aim of this study was to observe maternal, perinatal, and neonatal outcomes of pregnancies in which pRBCX was. METHOD: This was a single-center, retrospective, cross-sectional study, which recruited 46 consecutive adult pregnant women with SCD between January 2012 and June 2019. Obstetric features, SCD-related complications, and fetomaternal outcomes were compared between the 27 patients who received prophylactic exchange and the 19 who did not (therapeutic exchange was performed in 7 and was not performed in 12 cases). RESULTS: Painful crises, preeclampsia, and preterm birth rates were significantly higher in the group that did not receive prophylactic exchange (control group; P = .001, P = .024, and P = .027, respectively). There was one maternal mortality in the control group (P = .41). Incidence of adverse fetal or maternal complications was significantly higher in the control group (P = .044 and P = .007, respectively). CONCLUSIONS: Our center's experience over a 7.5-year period, as described above, demonstrates that pRBCX in SCD affects the course of pregnancy positively by ameliorating negative fetomaternal outcomes.

The Impact of the Ferric Carboxymaltose on Hemoglobin and Ferritin Levels.

BACKGROUND: Anemia is a frequent disorder worldwide. Iron deficiency anemia (IDA) is the most common form of anemia. Although oral iron is the first choice for treatment, the efficacy of oral iron preparations may be limited. Ferric carboxymaltose (FCM) is a novel parenteral iron preparation which can rapidly replenish iron stores. The aim of the present study is to investigate the impact of FCM dose on hemoglobin (Hb) and ferritin levels and the frequency of hypersensitivity reactions. METHODS: This study was conducted with 765 IDA patients between September 1, 2016 and September 1, 2018. He-moglobin (Hb), serum ferritin, transferrin saturation values were examined at the time of diagnosis, Hb and ferritin values at first month. RESULTS: Post-treatment Hb and ferritin levels significantly increased. The mean Hb level alteration was 2.43 ± 1.2 g/dL, the median ferritin level alteration was 157.3 ng/mL. The mean Hb level was lower and the mean change in Hb level was higher in higher doses. Allergic reactions were more frequent in higher doses. CONCLUSIONS: Ferric carboxymaltose is a novel treatment option with a low risk of hypersensitivity reactions and well tolerated even in high doses.

A Comparison of the BEAM and MITO/MEL Conditioning Regimens for Autologous Hematopoietic Stem Cell Transplantation in Hodgkin Lymphoma: An Analysis of Efficiency and Treatment-Related Toxicity.

BACKGROUND: Approximately half of patients with relapsed chemosensitive disease achieve robust responses with BEAM (BCNU, etoposide, cytarabine, and melphalan) and autologous stem cell rescue. The scarcity of comparative studies further limits alternative treatment protocols, such as the MITO/MEL (mitoxantrone, melphalan) protocol. PATIENTS AND METHODS: In this retrospective multicenter study, we compared the BEAM and MITO/MEL regimens used before autologous hematopoietic stem cell transplantation (ASCT) in terms of efficacy and side effects in patients with Hodgkin lymphoma. Data met international accreditation rules. Before ASCT, 108 patients received the MITO/MEL, and 34 patients received the BEAM. RESULTS: The median follow-up time was 36 months in the MITO/MEL group (range, 3-178) and 23 months in the BEAM group (range, 4-99). After ASCT, the 3-year expected overall survival and disease-free survival rates were 86.1% and 86.1% for the MITO/MEL group and 91.3% and 76.5% for the BEAM group, respectively. Although 50% of patients developed febrile neutropenia attacks in the MITO/MEL group, this rate was 91.1% in the BEAM group. The grade II and higher rates of hepatic, renal, gastrointestinal, and cardiac toxicities were similar in both groups. However, the rate of pulmonary toxicity was determined to be 1.9% in the MITO/MEL group and 29.4% in the BEAM group (P < .001). CONCLUSION: The MITO/MEL conditioning regimen seems to be as effective as the BEAM regimen but has better tolerability in terms of pulmonary toxicity and may be used as an alternative option if necessary, depending on the comorbidity status of the patient.

A Prospective Study on Dissociative Experiences, Suicidal Ideation, and Predicting Factors During the Isolation Period of Hematopoietic Stem Cell Transplant.

OBJECTIVES: The aim of the present study was to investigate suicidal ideation and dissociative experiences and to predict demographic and clinical risk factors during isolation periods in patients undergoing hematopoietic stem cell transplant. MATERIALS AND METHODS: Our study included 61 consecutive stem cell recipients (29 autologous, 32 allogeneic). Patients were evaluated with the Suicidal Ideation Scale, Dissociative Experiences Scale, Hamilton Depression Scale, Hamilton Anxiety Scale, and State Trait Anxiety Inventory. RESULTS: The transplant procedure did not influence the Dissociative Experiences or Suicidal Ideation Scales (P > .05). However, patients had higher anxiety and depression levels at time of discharge (P < .001). Suicidal ideation scores were correlated with higher Hamilton Depression Scale, State Trait Anxiety Inventory, and Dissociative Experiences Scale scores on admission (P < .05), with the latter 2 scores also higher at the time of discharge in patients who received radiotherapy prior to transplant (P < .05). CONCLUSIONS: Suicidal ideation and dissociative experiences, which may emerge because of complex and traumatic processes, should be considered by clinicians. Social and psychological support should be provided for patients undergoing hematopoietic stem cell transplant.

Significance of Lymphocyte Count, Monocyte Count, and Lymphocyte-To-Monocyte Ratio in Predicting Molecular Response in Patients with Chronic Myeloid Leukemia: a Single-Centre Experience.

BACKGROUND: Chronic myeloid leukemia (CML) is a disease resulting from BCR-ABL gene fusion. It is possible to monitor treatment by molecular testing for BCR-ABL. The lymphocyte-to-monocyte ratio (LMR) is a commonly used marker associated with prognosis in various neoplasms. This study was performed to evaluate the relevance of absolute lymphocyte count (ALC), absolute monocyte count (AMC), and LMR in predicting molecular response status in patients with chronic phase CML. METHODS: Samples submitted to our hematology laboratory for BCR-ABL testing between April 2012 and October 2018 were retrospectively reviewed. Concurrent hemogram testing together with the results of quantitative reverse transcriptase-polymerase chain reaction were noted. Data were grouped according to molecular response status and the ALC, AMC, and LMR were compared among patient groups. RESULTS: A total of 224 samples from 95 patients were included in the study. Analysis revealed differences between groups when newly diagnosed patients were compared with patients undergoing treatment, regardless of response status. However, analyzing the groups according to molecular response status failed to reveal differences in ALC, AMC, or LMR. CONCLUSIONS: ALC, AMC, and LMR are not potential biomarkers for predicting molecular response status in patients with chronic phase CML.