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Fanconi anemia (FA) is a rare and complex genetic disorder, clinically characterized by bone marrow failure, congenital defects, and cancer predisposition. Hematopoietic stem cell transplantation (HSCT) represents the only therapeutic option to restore normal hematopoiesis after the occurrence of marrow failure or clonal hematopoietic abnormality. However, radiation exposure during transplant may increase the risk of later malignancies. In this retrospective study, we analyzed the results of HSCT with a radiation-free, busulfan-based conditioning regimen in FA patients. A total of 122 patients (median age: 8 years, range: 2-18 years) with FA who underwent HSCT between January 2008 and January 2020 were enrolled in this study and followed up to the end of 2020. The preparative regimen included busulfan (0.2 mg/kg/day, days -9 to -6), cyclophosphamide (15 mg/kg/day, days -5 to -2), and in vivo T-cell depletion with rabbit anti-thymocyte globulin. All patients received graft-versus-host disease prophylaxis with cyclosporine combined with methotrexate. We used the Kaplan-Meier method, log-rank test, and Cox proportional hazards models to analyze patient survival. Peripheral blood, bone marrow and cord blood hematopoietic stem cells were used in 84 (68.9%), 31 (25.4%) and 7 (5.7%) patients, respectively. Donors were matched siblings in 48 (39.3%), matched other relatives in 56 (45.9%), and matched unrelated persons in 18 (14.8%) patients. With a median follow-up time of 24.25 months, graft rejection occurred in only one patient. The 1- and 5-year overall survival rates were 84.14% (95% confidence interval: 76.02-89.70) and 82.16% (95% confidence interval: 73.01-88.45), respectively. Of the patient characteristics documented before transplant, the presence of cardiopulmonary, genitourinary tract, central nervous system, and limb malformations significantly affected survival rates. Our results indicate excellent outcomes in patients with FA undergoing HSCT with a radiation-free, busulfan-based conditioning regimen. It would be desirable to aim at optimizing the outcome of HSCT in FA patients in future studies.

BackgroundCancer imposes a significant economic burden on the health system and society. Acute myeloid leukemia (AML) is the third deadliest leukemia and is one of the leading health problems worldwide. The present study aims to estimate the economic burden of AML in Iran for 2020.MethodsIn this study, we estimated a prevalence-based on the cost-of-illness of the AML in Iran. A societal perspective was considered, in which the direct costs and productivity losses with the adoption of the human capital approach in the AML cases were estimated for 2020. Moreover, in the present study, several resources including national cancer registry reports, hospital records, occupational data, and interviews with experts were cited.ResultApproximately 98% of patients with AML received induction therapy. The AML economic burden was $ 33243107.39. Indirect costs accounted for 60% of this amount, and direct medical costs made up for 19% of this estimated economic burden.ConclusionThe economic burden of AML in Iran is very significant and due to the increasing prevalence of this disease, it is expected to increase more gradually. Awareness of the costs associated with this disease provides a great opportunity for policymakers and managers of the health systems to improve resource allocation efficiently.

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Background: The first cases of proved COVID-19 in Iran were reported in February 2020 and has since rapidly spread worldwide. We aimed to clarify the clinical significance of hematologic parameters alteration in COVID-19. Methods: Different hematologic parameters were measured in 225 hospitalized COVID-19 patients in a tertiary care university hospital, during the peak of COVID-19 outbreak and their association with duration of hospitalization, ICU admission and especially mortality was analyzed. Results: Among a total of 225 patients, 24.4% did not survive after admission. Lymphopenia and neutrophilia were observed in 52.7% and 21.4% of the patients, respectively. The mean count of neutrophils was significantly higher in non-survived patients (P = .032). Elevated neutrophil-to-lymphocyte ratio (NLR) was significantly associated with mortality (P < .001). Low hemoglobin (Hb) concentration significantly correlated with mortality (P = .004) and ICU admission (P = .04). Platelet (Plt) count was significantly lower in the non-survived patients (P = .023). Non-survivors had significantly lower nadir Hb and Plt counts than survivors (P < .001 in both parameters). Platelet-to-lymphocyte ratio (PLR) also correlated with mortality and was significantly higher in non-survivors (P = .034). Conclusions: Hematologic laboratory parameters have always been a crucial component of diagnostic and therapeutic strategies in infectious disease. Hematologic predictors of a fatal outcome in COVID19 hospitalized patients in our series include elevated NLR and PLR, lower than normal Hb and Plt, elevated d-dimer and prolonged prothrombin time (PT), together with elevated inflammatory indicators in the blood.

BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment for acute leukemia. Many different parameters have significant impact on the final results of HSCT such as donor type, stem cell source, and the implemented conditioning regimen. In the absence of an HLA-matched related donor, unrelated donors or haploidentical donors are possible alternatives for patients with an indication to HSCT. In order to compare the outcomes of HSCT from different donor types, in this single-center study, using a radiation-free MAC regimen, we compared the results of unmanipulated peripheral blood stem cell transplantation (PBSCT) from matched and mismatched related and unrelated donors with haploidentical donors in the children, adolescents and young adults (CAYA) affected by acute leukemia.MethodsIn this retrospective study, since 2014 to 2021, the outcome of CAYA patients with acute leukemia who had undergone peripheral blood T cell-replete HSCT from haploidentical donors versus unrelated donors (including 10/10 or 9/10 HLA-matched) versus related donors (including 10/10 or 9/10 HLA-matched) were evaluated. The HSCT was based on a radiation-free MAC regimen including Busulfan and Cyclophosphamide. The GvHD prophylaxis was based on the administration of Cyclosporine A in all patients, plus rabbit anti-human thymocytes globulins in unrelated and haploidentical donors and post transplantation cyclophosphamide in haploidentical donors. Adjusted multivariable proportional hazard Cox and competing risk analyses were performed.ResultsMedian follow up time was 28.7 months (95% CI: 21.9-34.9). Three-year overall survival rate (OS) and GvHD-free/relapse-free survival (GFRFS) rate was 68.81% (95% CI: 60.08%-76.01%) and 44.19% (95% CI: 35.52%-52.49%), respectively. Patients who had undergone HSCT from an unrelated donor had the lowest OS and GFRFS compared to other donor types. The 3-years NRM in all patients was 7.84% (95% CI 4.36-12.62). Adjusted multivariable modeling of OS showed that the hazard of death in patients who had undergone HSCT from an unrelated donor, was 3.6 times more than patients who underwent HSCT from their haploidentical donors (P=0.05). Likewise, the hazard of NRM after HSCT from unrelated donors was 6 times more than haploidentical donors (P=0.002). However, the relapse incidence was not significantly different between the two mentioned groups.ConclusionsIn this study, HSCT from haploidentical donors was associated with superior survival rates compared to HSCT from unrelated donors. So haploidentical peripheral blood derived HSCT could be a practical and valuable clinical option that offers CAYA patients with acute leukemia needing HSCT and lacking matched available donors, a reasonable opportunity for disease control.

Background: Acute myeloid leukemia (AML) is the second common leukemia (5.18%) and the third deadliest leukemia in Iran. Moreover, it is the fifth prevalent cancer in the world, which involves 8% of all cancers. Objectives: The aim of this study was to calculate direct medical and non-medical costs of AML in 2019. Methods: The present retrospective-descriptive analysis was conducted on 192 patients with AML aged 19 to 70 years from 2016 to 2018. The data were collected from hospital records and interviews with experts. The bottom-up micro-costing approach and payer perspective was considered for cost analysis status. The relationship of affective variables was investigated, using nonparametric tests, including Mann–Whitney and Kruskal–Wallis tests. Costs were divided into costs of diagnosis, hospitalization, medication, nursing, visit and consultation, operating room, and medical supplies. The data were described by mean ± standard deviation and reported by percentage and also analyzed by SPSS 11 software. Results: According to the findings, the average age of all patients was 43.91 years and 55.7% of the patients were male. The highest and the lowest diagnostic costs were associated with laboratory tests at $1656459.48 and ultrasound charges $4229.46, respectively. The total direct medical costs per patient were $1056624.78 with an average of $4846.90 and the cost of medication included 36% of the total costs. The direct medical and non-medical costs were $10485488.48 and $487522.87, respectively Conclusions: Costs of AML treatment were estimated to be $1056624.78. Finally, it can be concluded that the cost of AML in Iran is much cheaper than that compared to other countries and also due to hidden subsidies from the public sector, the payment from the patient's pocket is very small.

Microvesicles (MVs) derived from bone marrow niche components have an important role in genetic reprogramming and subsequent drugs induce apoptosis in leukemic cells. Here, we have found that undertreatment of curcumin or daunorubicin, the cross-talk through MVs of KG-1-bone marrow mesenchymal stem cells (BMSCs), significantly downregulates the expression of the survival gene osteopontin (OPN), CXCL-12, IL-6 (interleukin-6), STAT-3, and VCAM-1 (vascular cell adhesion molecule 1) in treated-KG-1 cells as well as exclusively upregulates CXCL-12 in BMSCs. Drug treated-cell populations' MVs of both single cultured osteoblasts (OBs) and cocultured KG-1 + BMSCs + OBs similarly upregulate survival mediators' OPN, CXCL-12, IL-6, STAT-3, and VCAM-1 in treated-KG-1 cells. Likewise, isolated MVs from KG-1 cells or communication between KG-1, BMSCs, and OBs treated by drugs increase the expression of genes OPN, CXCL-12, IL-6, STAT3, and VCAM-1 by OBs. MVs derived from KG-1 + BMSCs + OBs reduce drug-induced apoptosis in KG-1 cells. This suggests MVs-mediated information transfer is a procedure whereby OBs could overcome BMSCs-induced apoptosis in drug-treated-KG-1 cells.

Background: In the evolution of haploidentical stem cell transplantation (haplo-SCT), the implementation of anti-thymocyte globulin (ATG)-based and high-dose posttransplant cyclophosphamide (PTCy)-based regimens has improved patient outcomes. We hypothesized that the combination of ATG and PTCy in the correct sequence and with proper timing has a synergistic effect on immune tolerance. The purpose of the study was to discover whether the concomitant use of ATG and PTCy would be advantageous for haplo-SCT and which subgroup of patients would receive the most benefit.Methods: This cohort was conducted on 119 patients with poor prognosis acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) who underwent haplo-SCT with peripheral blood stem cell (PBSC) sources and myeloablative conditioning (MAC) regimens using a uniform protocol in our center from 2010 to 2019. The outcomes of patients who received a combination of rabbit ATG (2.5 mg/kg/d for three days) plus modified PTCy (40 mg/kg/d on days +3 and +4) (n=100) was compared with those of patients who received an ATG-only regimen (n=19). The median follow-up was 35.8 months. Both arms shared similar characteristics, except for the median donor age, the distribution of relationships, and the median time between diagnosis and transplantation.Results: The cumulative incidence of acute graft versus host disease (aGvHD) grade II-IV was significantly lower in the ATG-PTCy group (P < 0.0001), although the incidence of 30-day neutrophil engraftment was higher in the ATG group (P = 0.036). The overall outcome was not significantly different between the two arms. Subgroup analyses stratified by disease status separately for AML and ALL indicated 3-year leukemia-free survival rates of 72% and 24.6% for the first remission of intermediate-high risk AML and ALL; 34.4% and 34.5% for recurrent disease; and 46% and 33.3% for refractory disease.Conclusion: Our experience indicates that the combination of ATG +PTCy in the context of MAC and PBSC sources offers satisfactory outcomes for patients with intermediate-high risk AML receiving haplo-SCT during the first remission; however, some modifications are recommended to improve the results of other subgroups.

BackgroundCOVID-19 has caused great concern for patients with underlying medical conditions. We aimed to determine the prognosis of patients with current or previous cancer with either a PCR-confirmed COVID-19 infection or a probable diagnosis according to chest CT scan.MethodsWe conducted a case control study in a referral hospital on confirmed COVID-19 adult patients with and without a history of cancer from February25thto April21st, 2020. Patients were matched according to age, gender, and underlying diseases including ischemic heart disease (IHD), diabetes mellitus (DM), and hypertension (HTN). Demographic features, clinical data, comorbidities, symptoms, vital signs, laboratory findings, and chest computed tomography (CT) images have been extracted from patients’ medical records. Multivariable logistic regression was used to estimate odd ratios and 95% confidence intervals of each factor of interest with outcomes.ResultsFifty-three confirmed COVID-19 patients with history of cancer were recruited and compared with 106 non-cancerous COVID-19 patients as controls. Male to female ratio was 1.33 and 45% were older than 65. Dyspnea and fever were the most common presenting symptoms in our population with 57.86 and 52.83% respectively. Moreover, dyspnea was significantly associated with an increased rate of mortality in the cancer subgroup (p = 0.013). Twenty-six patients (49%) survived among the cancer group while 89 patients (84%) survived in control (p = 0.000). in cancer group, patients with hematologic cancer had 63% mortality while patients with solid tumors had 37%. multivariate analysis model for survival prediction showed that history of cancer, impaired consciousness level, tachypnea, tachycardia, leukocytosis and thrombocytopenia were associated with an increased risk of death.ConclusionIn our study, cancer increased the mortality rate and hospital stay of COVID-19 patients and this effect remains significant after adjustment of confounders. Compared to solid tumors, hematologic malignancies have been associated with worse consequences and higher mortality rate. Clinical and para-clinical indicators were not appropriate to predict death in these patients.

Introduction: The COVID-19 pandemic has challenged hematopoietic stem cell transplant (HSCT) clinicians to profoundly re-organize their medical care to reduce complications without compromising patients’ inquiries. Since this pandemic is a foggy novel disease, scientific approved data are not available, and so decisions should be made based on expert opinions. Methods: This is a pediatric HSCT center experience, including preventive and solving strategies specifically undertaken to address problems caused by the COVID-19 outbreak. Results: In this report, we have shared our experience to alert healthcare professionals worldwide to get prepared accordingly. Conclusion: We are not aware of the duration or outcome of the pandemic, but we are intended to learn from our experiences and figure out the best strategies to minimize the possible harms.

The frontline treatment for patients younger than 40 years with severe aplastic anemia (AA) is allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-identical sibling donor. However, in patients with severe AA who are older than 40 years, allogeneic HSCT has been found to be associated with increased treatment-related mortality and toxicity, even when matched sibling donors are used. We report our institutional experience with allogeneic HSCT in patients with severe AA between 40 and 50 years. A total of 19 patients with severe AA were included in the study. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan–Meier method. The mean age of patients at the time of transplant was 43.79 years, and 57.9% were male. The mortality rate was 36.8%, attributed to infection (10.5%), relapse (15.8%), and renal failure (5.3%) in all cases. Acute graft-versus-host disease (GVHD) occurred in five patients (26.3%), and chronic GVHD occurred in two patients (10.5%). The 5-year OS was 62% and the 5-year DFS was 52%. We found that the patient's age, platelet level prior to transplantation, and the number of CD3 cells infused for each transplant were independent prognostic factors for OS, and the age and sex of the patient, graft rejection, and platelet level prior to transplantation were significant prognostic factors associated with DFS. We recommend that immunosuppressive therapy be considered as a first-line treatment in patients with severe AA who are older than 40 years. Allogeneic HSCT can be considered a valid alternative option in patients whose suppression therapy fails.

Background Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment for thalassemia major (TM). Infertility and its indicators have been assessed in transfusion dependent TM men, but in this study, we sought to compare the fertility indicators of TM patients after HSCT with those in patients treated conventionally. The possible influential factors on reproductive capacity in TM patients undergone allogeneic HSCT were also evaluated. Patients and methods In this cross-sectional study, we compared the gonadal hormones level, testicular volume, Tanner stage and sperm analysis in transfusion-dependent thalassemia major (TDTM) patients who survived matched sibling HSCT (n = 43) with patients conventionally treated by transfusion and iron chelation (n = 52). Results The patients’ age range was between 16 to 41 years. Tanner stage 4–5 was seen in 39 patients (41%). The prevalence of hypogonadism in our patients was 32.63% but its frequency was not significantly different between the two groups (p = 0.35). Azospermia, oligospermia, astenospermia, teratospermia and even having dry and low volume ejaculate were all significantly more frequent in the post-transplant patients compared to TDTM group. In the post-HSCT group, neither patients’ age at transplantation nor the conditioning regimen used in their transplant process did significantly affect their hormonal status and sperm parameters. Chronic graft versus host disease (GVHD) occurred in 14 (40%) patients. No significant difference was observed between the grade of chronic GVHD and hypogonadism (P = 0.853). Conclusions Thalassemia patients undergone allogeneic HSCT have lower fertility potential, mainly in sperm parameters compared with patients treated with blood transfusion and chelation. This information is important for thalassemic patients considering HSCT.

Background: Successful hematopoietic stem cell transplantation (HSCT) could cure the hematological manifestations of transfusion-dependent thalassemia (TDT), but introduces risks of morbidity and mortality. Umbilical cord blood transplantation (UCBT) is considered as an acceptable strategy, by providing a condensed graft versus host disease (GvHD). This paper compares the outcomes of UCBT with HSCT from peripheral blood and bone marrow in TDT patients.Methods: Between 1998 and 2014, 10 patients with TDT underwent UCBT, which were matched with 20 patients undergone BMSCT and 20 patients undergone PBSCT, by using propensity score matching (PSM) for age, gender and thalassemia class. All patients received the same myeloablative conditioning regimen and were transplanted from a fully HLA matched sibling donor. Results: The median follow-up time after HSCT was 5.7 years. Rejection incidence was 70.0% (95% CI = 28.1%-90.4%) after UCBT, 25.6% (95% CI = 8.9%-46.4%) after BMSCT, and no rejection occurred in the PBSCT group. Acute GVHD incidence was 20.0% (95% CI = 2.6%-49.0%), 35.0% (95% CI = 15.1%-55.8%), and 40.0% (95% CI = 18.6%-60.6%) in patients undergone UCBT, BMSCT and PBSCT, respectively (P=0.62). The incidence of chronic GVHD was 7.2% (95% CI = 0.3%-28.7%), and 35.2% (95% CI = 13.7%-57.8%) in patients undergone BMSCT and PBSCT, respectively (P=0.026) and none of the patients in the UCBT group experienced chronic GvHD. Conclusions: Although the overall survival is not significantly influenced by the graft source, due to the high incidence of rejection after UCBT, the probability of thalassemia free survival is very low in these patients.

Background:COVID-19 has been declared as a public health emergency and a pandemic by World Health Organization. Among high-risk patients infected by the virus, hematopoietic stem cell transplant (HSCT) recipients are vulnerable to severe presentation of this infection. Thus, the necessity for precise strategies in dealing with HSCT recipients in this pandemic seems inevitable. Methods: We discussed the dilemmas brought up by the emergence of COVID-19 in the management of HSCT recipients, through a virtual panel of experts, considering the latest available records about COVID-19. About each enquiry, we have provided the consensus of the clinicians and paraclinicians in our center. Recommendations: We agreed to choose more precautious strategies and less optimal policies. The amendments aim to reduce the risk of exposure to COVID-19 in our patients and also in our health care provider team.