Donor lymphocyte infusions: An experience from a tertiary care center of North India.

Donor lymphocyte infusions (DLIs) are often recommended products after allogeneic hematopoietic stem cell transplant to increase graft - versus - leukemia effect. More success rate of DLI has been reported in relapsed posttransplant chronic myeloid leukemia. Whatever the indication for DLI, mortality related to post-DLI infusion is 5%-20%, and more than one-third of patients will develop acute and/or chronic graft versus host disease (GVHD) after DLI. We report two cases where DLIs were used for residual disease after posttransplant. Both of DLI went uneventful. None of the patient's developed signs of GVHD postinfusion. Although both patients expired with different causes, none were related to DLI infusion. Information from published literature suggests that DLI should be administered early after relapse or as a prophylactic strategy in patients receiving T-cell-depleted grafts, and patients with aggressive diseases may benefit from disease reduction before DLI. However, further evidence is required to evaluate its efficacy, especially in relapsed or residual hematological malignancies.

Challenges in the transfusion management of a 15-month-old pediatric patient with Bombay blood group phenotype.

Bombay blood group phenotype is often mistyped as O group which can lead to hemolytic transfusion reactions. There are a very few case reports of Bombay blood group phenotype in pediatric age group. Herein, we report an interesting case of Bombay blood group phenotype in a fifteen-month-old pediatric patient who presented with features of raised intracranial pressure and required an emergency surgery. The Bombay blood group was detected on detailed immunohematology work up which was further confirmed by molecular genotyping. The challenges faced in developing countries for transfusion management of such a case have been discussed.

Impact of buffy coat reduction on the severity of febrile nonhemolytic transfusion reactions with red cell components.

BACKGROUND: Febrile nonhemolytic transfusion reactions (FNHTRs) are the most common adverse reaction reported under the Haemovigilance Programme of India, and the use of leukodepleted blood products is recommended. The severity of the reaction may affect the morbidity associated with the reaction. This study aims to calculate the incidence of various transfusion reactions in our blood center and to evaluate the impact of buffy coat reduction on the severity of febrile reaction and other hospital resource-consuming activities. MATERIALS AND METHODS: It was an observational retrospective study in which all reported FNHTRs were evaluated during the period July 1, 2018-July 31, 2019. Patient demographic details, component transfused, and clinical presentation were analyzed to identify factors affecting the severity of FNHTRs. RESULTS: The incidence of transfusion reaction in our study period was 0.11%. Out of total 76 reactions reported, 34 (44.7%) were febrile reactions. Other reactions included allergic reactions (36.8%), pulmonary reactions (9.2%), transfusion-associated hypotension (3.9%), and others (2.7%). The incidence of FNHTR in buffy coat-depleted packed red blood cells (PRBCs) and PRBCs is 0.03% and 0.05%, respectively. FNHTRs are seen more in females with prior history of transfusion (87.5%) as compared to males (66.67%) (P = 0.046). We also found that FNHTRs are less severe with buffy coat-depleted PRBC transfusion than PRBC transfusion as mean ± standard deviation temperature rise was less in buffy coat-depleted PRBC (1.3 ± 0.8) than PRBC (1.74 ± 1.129). The febrile response to buffy coat-depleted PRBC transfusion occurred at higher volume (145 ml) transfusion than PRBC transfusion (87.2 ml), and it was statistically significant (P = 0.047). CONCLUSION AND SUMMARY: Leukoreduction remains the main modality to prevent FNHTR, but in developing countries like India, the use of buffy coat-depleted PRBC over PRBC can reduce the incidence and severity of FNHTR.

Effectiveness of therapeutic plasma exchange in case of rare neurological disorder Isaacs syndrome.

Isaacs syndrome is a disease characterized by nerve hyperexcitability and pseudomyotonia and treated with immunomodulatory and symptomatic therapy approaches. Here, we report a case of anti-(leucine-rich glioma-inactivated 1) antibody-positive patient diagnosed as Isaacs syndrome and accomplished a nearly complete response to only four sessions of therapeutic plasma exchange (TPE). Our experience suggests that TPE along with other immunomodulatory agents may be beneficial and well-tolerated approach in patient with Isaacs syndrome.

Therapeutic plasma exchange is a safe and effective bridge therapy in patients with alcohol-associated ACLF not having immediate prospects for liver transplantation-A case-control, pilot study.

BACKGROUND: Therapeutic plasma exchange (TPE) is a well-established treatment modality in acute liver failure patients, but its efficacy in treating acute on chronic liver failure (ACLF) patients is yet to be established. AIM: To assess the efficacy and safety of TPE in patients with alcohol-associated ACLF who were nonresponders to standard medical treatment (SMT) and without immediate prospects for liver transplantation. METHODS: Twenty-eight alcohol-related ACLF (grade II) patients (14 cases and 14 controls) were enrolled in the study. Cases underwent standard volume TPE along with SMT while the controls were on SMT alone. The change (baseline to day 10) in laboratory parameters, cytokine concentrations, clinical severity scores along with 30 and 90 day mortality rates were noted and compared between the two groups. The adverse events (AEs) were noted in the groups and analyzed. RESULTS: A total of 51 TPE procedures were performed in 14 patients (average of 3.62 procedures/patient). TPE was effective in reduction of serum bilirubin, ammonia, activated partial thromboplastin time, prothrombin time, international normalized ratio, and severity scores (ACLF Research Consortium, Maddrey's discriminant function, and model for end-stage liver disease) (P < .05). There was no significant difference in the reduction of serum interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α concentrations among cases. Among the cases who received the complete TPE interventions, 30- and 90-day mortality rates were lower in the cases as compared to controls albeit only the 90-day mortality was significantly different. Procedure-related AEs was observed in 2% of procedures. CONCLUSION: TPE is an effective and well-tolerated bridge therapy in patients with alcohol-associated ACLF of moderate severity not improving on SMT and without immediate prospects for liver transplantation.

Multiple cycles of granulocyte colony-stimulating factor in decompensated cirrhosis: a double-blind RCT.

BACKGROUND: Liver transplant, the definitive treatment of decompensated cirrhosis (DC), is constrained by donor shortage and long-term complications. Granulocyte colony-stimulating factor (G-CSF) has been explored as an alternative option in open-label studies. This double-blind, randomized, placebo-controlled trial was designed to elucidate the efficacy of G-CSF in DC. METHODS: Seventy patients were randomized to either G-CSF plus standard medical therapy (group A, n = 35) or placebo plus standard medical therapy (group B, n = 35). Primary outcome was 12-month overall survival in patients who received at least one cycle of intervention. Secondary outcomes were mobilization of CD34+ cells at day 6, improvement in Child-Turcotte-Pugh (CTP), and model for end-stage liver disease (MELD), liver stiffness measurement, quality of life, nutrition, hepatic decompensation, infection, hospitalization, and acute kidney injury. RESULTS: Survival in group A was higher than that in Group B although the difference was not statistically significant (87.9% vs 66.7%; p = 0.053). CD34+ cells at day 6 were significantly higher in group A as compared to baseline (p < 0.001). Ascites control (p = 0.03) and CTP score improvement (p = 0.02) were better in group A at 12-months. Encephalopathy episodes (p = 0.005), infections (p = 0.005) were fewer in group A than group B at 12 months. Other secondary outcomes did not improve post-therapy. There were no treatment-related discontinuations or severe adverse events. CONCLUSIONS: G-CSF therapy is safe. The improvement in survival at 12 months is not statistically significant. Better control of ascites, improvement of CTP score, fewer encephalopathy episodes and decreased rate of infections were observed with G-CSF therapy (NCT03911037). Trials Registration NCT03911037.

Buffy coat pooled platelet concentrate: A new age platelet component.

BACKGROUND: Buffy coat pooled platelet concentrate (BCPP) is a new blood component mainly used in Europe, which has good attributes of both random donor platelets and apheresis platelets in terms of high platelet count, leukoreduced and available in emergency. We planned this study to compare quality parameters and biochemical activation markers among buffy coat pooled platelets and apheresis platelet concentrate (AP-PC) to establish the quality and safety of this new blood component during storage. MATERIALS AND METHODS: Three different preparations of BCPP were prepared: Nonleukoreduced (BCPP Part A), leukoreduced (BCPP Part B), and leukoreduced with platelet additive solution (PAS) (BCPP Part C) using a pool of 15 ABO-matched, nonreactive buffy-coats in each experiment to avoid any donor-related variations. Ten such experiments were done. Each BCPP was equivalent to 5 buffy coat units. Ten apheresis platelets were taken as control. Serial samplings were done on day 0, 3, and 5 of collection and were assessed for: volume, platelet count, white blood cell count, swirling, pH, sterility, glucose, lactate, soluble p-selectin, Interleukin (IL)-6, IL-1 ß, and tumor necrosis factor alpha (TNF-α). RESULTS: BCPP Part C (leukoreduced with PAS) maintained the best quality parameters in terms of maintenance of pH, least lactate accumulation, least sP-selectin levels, and least accumulation of inflammatory mediators (IL-6, IL-1 ß, and TNF-α) than the other groups >BCPP part B >AP-PC and >BCPP Part A. On day 5 of storage pH for BCPP Part A, Part B, Part C, and AP-PC was: 6.33, 6.42, 6.64, and 6.29, respectively, and soluble p-selectin (ng/ml) was 201 ± 22, 186 ± 11, 149 ± 18, 200 ± 23, respectively. BCPP Part B and AP-PC had comparable quality parameters and activation markers. CONCLUSIONS: Buffy coat pooled platelet has comparable and even better-quality control parameters (especially leukofiltered with PAS) than conventional platelet preparation and is a good alternative for meeting platelet transfusion requirements of critical patients during emergency hours in resource-constraint setting.

Autologous stem cell transplant for high-risk neuroblastoma: Achieving cure with low-cost adaptations.

BACKGROUND: The majority of patients in low- and middle-income countries (LMIC) are unable to receive optimal therapy, including autologous stem cell transplant (ASCT) for high-risk neuroblastoma. Management is intensive and multidisciplinary; survival is often poor. We report a single-center outcome of high-risk neuroblastoma, with adaptations optimized for LMIC. PROCEDURE: The study was retrospective. Patients were treated on the backbone of the high-risk neuroblastoma study-1 of SIOP-Europe (HR-NBL1/SIOPEN) protocol with ASCT. Adaptations incorporated to decrease cost, requirement for inpatient admission, infections, and faster engraftment included (a) optional outpatient administration for rapid-COJEC, (b) two sessions of stem-cell apheresis, (c) storing stem cells at 2-6°C without cryopreservation for up to 7 days, (d) no central lines, (e) no antibacterial/antifungal/antiviral prophylaxis, (f) omitting formal assessment of cardiac/renal/pulmonary functions before ASCT, and (g) administration of pegylated granulocyte colony-stimulating factor on Day +4. RESULTS: Over 5 years 9 months, 35 patients with high-risk neuroblastoma were treated. Rapid-COJEC was administered over a median duration of 80 days (interquartile range: 77, 83). Conditioning regimen included melphalan (n = 7), oral busulfan-melphalan (Bu/Mel; n = 6), or intravenous Bu/Mel (n = 22). The median viability of stem cells stored for 6 days (n = 28) was 93% (range: 88-99). Two (5.7%) patients had ASCT-related mortality. The 3-year overall and event-free survival was 41% and 39%, respectively. A relapse occurred in 20 (57%) patients. Treatment abandonment was observed in one (3%) patient. CONCLUSIONS: Administration of therapy in a disciplined time frame along with low-cost adaptations enables to manage high-risk neuroblastoma with low abandonment and an encouraging survival in LMIC. Stem cells can be stored safely without cryopreservation for up to 7 days.

Comparison of efficacy of low and high dose prophylactic platelet transfusion therapy in thrombocytopenic haemato-oncology patients.

INTRODUCTION: To determine an optimal platelet dose in thrombocytopenic patients is important for their judicious use. Transfusing platelets in different doses and comparing their post transfusion response can achieve this. AIM: To compare the efficacy of low and high dose single donor apheresis platelets (SDAP) with standard dose transfusions in terms of Corrected Count Increment (CCI), Percent Platelet Recovery (PPR) and transfusion free interval. METHOD: It was a prospective case control study done from January 2016 to April 2017. Twenty-eight hemato-oncology patients with CCI ≥5000 at 20-24 hours after standard dose (3 × 1011/unit), received low dose (1.5 × 1011 platelets/unit) and high dose (>4 × 1011 platelets/unit) SDAP. CCI and PPR were calculated after 20 to 24 hours of transfusion. Transfusion free interval and bleeding episodes were also noted. Grading was done according to WHO bleeding scale. RESULT: There was no statistical difference in CCI and PPR when standard dose was compared with low dose (CCI: p = 0.92, PPR: p = 0.89). When standard and high dose was compared, standard dose gave better results than the high dose in terms of CCI (p = 0.006) and PPR (p = 0.008) although the post transfusion increments were comparable (p = 0.938). High dose gave better (p = 0.005) platelet count increments than low dose but CCI (p = 0.04) and PPR (p = 0.05) was significantly less than the low dose. The difference in transfusion free intervals after three doses was not significant. Donor exposure to the patients was significantly (p = 0.000) reduced to 17.5%. CONCLUSION: Possibility of low dose as an alternative to standard dose can be considered in view of comparable platelet response indicators and significantly reduced donor exposure.

Efficacy of cross-match compatible platelets in multi transfused haemato-oncology patients refractory to platelet transfusion.

BACKGROUND: Platelet refractoriness, which leads to platelet transfusion failure resulting in significant morbidity and long hospital stay, is routinely not investigated. AIMS: To determine the efficacy of cross-match compatible platelets in multi-transfused alloimmunized hemato-oncological patients refractory to platelet transfusion. MATERIALS AND METHOD: 149 ABO compatible single donor apheresis platelet transfusions given to 38 alloimmunized refractory patients. Corrected Count Increment (CCI) <5000 (1 h) was taken to define refractoriness. Solid-phase red cell adherence assay was used to determine the alloimmunization status and platelet cross-matching. Post Transfusion Platelet Increment, CCI and the Percentage Platelet Recovery were used to monitor the effectiveness of platelet transfusion. ANOVA test followed by Post hoc test Tukey HSD used to compare group means and classified into three groups depending upon the cross-matching and compatibility status. Categorical data was analysed for various outcomes using Pearson's chi square test or Fischer exact test. RESULT: Patients showed statistically significant recovery in terms of PPI, CCI and PPR at 1 h post SDAP transfusions when they received cross-matched compatible platelets. The one-hour CCI was significantly higher for cross-match-compatible platelets (19173 ±â€¯2692) than for incompatible (5888 ±â€¯1526) and for uncross-matched (8140 ±â€¯1480). Forty four (97.8%) of 45 cross-matched compatible platelet transfusion episodes showed a satisfactory response in terms of PPI and CCI values as compared to 50 % and 53.9% in uncross-matched group respectively (p < 0.0001). CONCLUSION: Platelet cross-matching is an effective intervention in the management of multi-transfused alloimmunized Haemato-oncological patients, refractory to platelet transfusion.

A Study on the Effect of Pre-donation Salt Loading on Vasovagal Reactions in Young College Going Whole Blood Donors.

INTRODUCTION: The pathophysiology of vasovagal reactions (VVRs) involves both psychological and physiological components. Strategies which could allay physiological changes include interventions like pre-donation water intake and applied muscle tension have been published, however salt loading has not been tested. MATERIALS AND METHODS: Cross sectional study enrolling 1000 young college going whole blood donors with intervention 250 ml of salted loaded water or plain water as placebo. The immediate VVRs were recorded with respect to age, gender, donation status, blood volume, blood volume drawn and BMI. RESULTS: VVRs occurred in 25 out of 1000 (2.5%) young college going whole blood donors. Overall there were 18 VVRs in 526 (3.4%) donors in the placebo arm compared to 7 in 474 (1.5%) in salt loaded arm with odds of 2.36 (p = 0.049), however the difference in means of VVRs between the study arms could not achieve statistical significance on binary logistic regression. The independent risk factors including age, gender, blood volume, blood volume withdrawn and BMI or the donation status were not found to be effect modifiers on the occurrence of VVRs. CONCLUSION: Salt loading before blood donation in young college going whole blood donors does decrease the VVRs in the immediate post donation period; however the decrease was limited to a trend and could not attain statistical significance.

Autologous bone marrow-derived mononuclear cells transplantation in type 2 diabetes mellitus: effect on ß-cell function and insulin sensitivity.

BACKGROUND: Insulin resistance and insulin deficiency are the cardinal defects in the pathogenesis of type 2 diabetes mellitus (T2DM). Despite the plethora of anti-diabetic medications, drugs specifically targeting the ß-cells are still desired. Stem cell therapy has emerged as a novel therapeutics strategy to target ß-cells; however, their mechanism of action has not been well defined. This study aims to examine the efficacy and safety of autologous bone marrow-derived mononuclear cells (ABM-MNCs) transplantation in T2DM, and explores the mechanistic insights into stem cells action through metabolic studies. METHODS: Seven T2DM patients with the duration of disease ≥5 years, receiving triple oral anti-diabetic drugs along with insulin (≥0.4 IU per kg per day) and HbA1c ≤ 7.5% (≤58.0 mmol/mol) were enrolled for ABM-MNCs administration through a targeted approach. The primary end-point was a reduction in insulin requirement by ≥50% from baseline, while maintaining HbA1c < 7.0% (<53.0 mmol/mol) with improvement in insulin secretion, and/or insulin sensitivity after ABM-MNCs transplantation. RESULTS: Six out of 7 (90%) patients achieved the primary end-point. At 6 months, there was a significant reduction in insulin requirement by 51% as compared to baseline (p < 0.003). This was accompanied by a significant increase in the 2nd phase C-peptide response during hyperglycemic clamp (p = 0.018), whereas there were no significant alterations in insulin sensitivity and glucose disposal rate during hyperinsulinemic-euglycemic clamp relative to the baseline. Other measures of ß-cell indices like HOMA-ß, and stimulated C-peptide response to glucagon and mixed meal tolerance test were non-contributory. CONCLUSION: ABM-MNCs transplantation results in significant reduction in insulin doses and improvement in C-peptide response in patients with T2DM. Metabolic studies may be more useful than conventional indices to predict ß-cell function in patients with advanced duration of T2DM. Trial registration-Clinicaltrials.gov NCT01759823.

Efficacy of Autologous Bone Marrow-Derived Mesenchymal Stem Cell and Mononuclear Cell Transplantation in Type 2 Diabetes Mellitus: A Randomized, Placebo-Controlled Comparative Study.

Drugs targeting ß-cells have provided new options in the management of T2DM; however, their role in ß-cell regeneration remains elusive. The recent emergence of cell-based therapies such as autologous bone marrow-derived mesenchymal stem cells (ABM-MSCs) and mononuclear cells (ABM-MNCs) seems to offer a pragmatic approach to augment ß-cell function/mass. This study aims to examine the efficacy and safety of ABM-MSC and ABM-MNC transplantation in T2DM and explores alterations in glucose-insulin homeostasis by metabolic studies. Thirty patients of T2DM with duration of disease ≥5 years, receiving triple oral antidiabetic drugs along with insulin (≥0.4 IU/Kg/day) with HbA1c ≤7.5%(≤58.0 mmol/mol), were randomized to receive ABM-MSCs or ABM-MNCs through targeted approach and a sham procedure (n = 10 each). The primary endpoint was a reduction in insulin requirement by ≥50% from baseline, while maintaining HbA1c <7.0% (<53.0 mmol/mol) during 1-year follow-up. Six of 10 (60%) patients in both the ABM-MSC and ABM-MNC groups, but none in the control group, achieved the primary endpoint. At 12 months, there was a significant reduction in insulin requirement in ABM-MSC (P < 0.05) and ABM-MNC groups (P < 0.05), but not in controls (P = 0.447). There was a significant increase in second-phase C-peptide response during hyperglycemic clamp in the ABM-MNC (P < 0.05) group, whereas a significant improvement in insulin sensitivity index (P < 0.05) accompanied with an increase in insulin receptor substrate-1 gene expression was observed in the ABM-MSC group. In conclusion, both ABM-MSCs and ABM-MNCs result in sustained reduction in insulin doses in T2DM. Improvement in insulin sensitivity with MSCs and increase in C-peptide response with MNCs provide newer insights in cell-based therapies.

Successful Management of Refractory Dialysis Independent Wegener's Granulomatosis with Combination of Therapeutic Plasma Exchange and Rituximab.

Wegeners granulomatosis (WG) is an autoimmune, antineutrophil cytoplasmic antibody mediated necrotizing vasculitis involving renal, and upper and lower respiratory systems. Treatment relies on a combination of immunosuppressive drugs and tapering regimen of glucocorticoids. Therapeutic plasma exchange (TPE) has been recognized as a second line treatment. We report the successful use of TPE in combination with rituximab in achieving remission in a patient with WG (dialysis independent) not responding to conventional therapy.

The role of comprehensive check at the blood bank reception on blood requisitions in detecting potential transfusion errors.

Pre-transfusion testing includes proper requisitions, compatibility testing and pre-release checks. Proper labelling of samples and blood units and accurate patient details check helps to minimize the risk of errors in transfusion. This study was aimed to identify requisition errors before compatibility testing. The study was conducted in the blood bank of a tertiary care hospital in north India over a period of 3 months. The requisitions were screened at the reception counter and inside the pre-transfusion testing laboratory for errors. This included checking the Central Registration number (C.R. No.) and name of patient on the requisition form and the sample label; appropriateness of sample container and sample label; incomplete requisitions; blood group discrepancy. Out of the 17,148 blood requisitions, 474 (2.76 %) requisition errors were detected before the compatibility testing. There were 192 (1.11 %) requisitions where the C.R. No. on the form and the sample were not tallying and in 70 (0.40 %) requisitions patient's name on the requisition form and the sample were different. Highest number of requisitions errors were observed in those received from the Emergency and Trauma services (27.38 %) followed by Medical wards (15.82 %) and the lowest number (3.16 %) of requisition errors were observed from Hematology and Oncology wards. C.R. No. error was the most common error observed in our study. Thus a careful check of the blood requisitions at the blood bank reception counter helps in identifying the potential transfusion errors.

Defining an appropriate leucoreduction strategy by serial assessment of cytokine levels in platelet concentrates prepared by different methods.

BACKGROUND AND OBJECTIVES: Different methods of platelet concentrate preparations leave behind certain number of residual leukocytes, accounting for most of the febrile nonhemolytic transfusion reactions, especially in multitransfused patients. Various inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 are generated during storage and have been implicated for these adverse effects. We have studied the levels of these cytokines and their correlation with leucocyte contents in platelet concentrates prepared by three different methods. STUDY DESIGN AND METHODS: Five pools of platelet rich plasma platelet concentrates (PRP-PC) and buffy-coat platelet concentrates (BC-PC) each were prepared and divided into two halves. One half of the pool was leucofiltered (LF), whereas the other half was stored as such. Ten apheresis units were also included in the study. All the platelet concentrates were assessed for leucocyte load and cytokine content (IL-1ß, IL-6, and TNF-α) on different days of storage (0, 3, and 5) using Nageotte chamber and commercially available immunoassays respectively. RESULTS: There was a statistically significant rise in cytokine levels (IL-1ß, IL-6, and TNF-α) in nonleucofiltered (NLF) random donor platelet concentrates (RDPs) (PRP-PC and BC-PC) during storage (day 3 and 5) whereas LF RDP concentrates (PRP-PC and BC-PC) and apheresis platelet concentrates (AP-PC) did not show any significant rise in cytokine levels (on day 3 and 5) over the baseline values at day 0. CONCLUSION: This data suggests that although AP-PCs are superior to PRP-PC (NLF) and BC-PC (NLF) in terms of in vitro quality control parameters and cytokine generation during storage, BC-PC mode of platelet preparation followed by leucofiltration is the best method to store platelets and minimise the cytokine accumulation. This strategy is best suited for transfusion in multitransfused hematooncologic patients, who cannot afford single donor apheresis platelets.

Prevalence of risk factors for platelet transfusion refractoriness in multitransfused hemato-oncological patients at tertiary care center in North India.

BACKGROUND: This study was designed to determine the prevalence and assess the risk factors responsible for platelet transfusion refractoriness in hemato-oncological patients. MATERIALS AND METHODS: The study included 30 patients. Twelve were clinically diagnosed as aplastic anemia and the 18 were of acute myeloid leukemia. A prospective 3 months follow-up was planned to monitor the response of platelet transfusion therapy, based on their posttransfusion corrected count increment at 1(st) and 24(th) h. Based on the observations, patients were categorized into refractory and nonrefractory groups. Common nonimmunological causes such as fever, sepsis, bleeding, disseminated intravascular coagulation, chemotherapy, splenomegaly, ABO mismatch, and antithymocyte globulin therapy were monitored. Among the immunological causes, presence of antihuman leukocyte antigen (HLA) class I antibodies and platelet glycoprotein antibodies in patient's serum were monitored. RESULTS: During the study period, 17 (56.66%) patients did not show desired platelet count increment. Transfusion requirements of refractory group for both red cell and platelet product were significantly higher (P < 0.05) in comparison to nonrefractory group. Among immunological causes, anti HLA class I antibodies (P < 0.013), antihuman platelet antigen-5b antibodies (P < 0.033) were significantly associated with refractoriness. Among nonimmunological causes, bleeding (P < 0.019, odd ratio 8.7), fever (P < 0.08, odd ratio 5.2), and infection (P < 0.07, odd ratio 5.4) were found to associated with refractoriness. CONCLUSION: Platelet refractoriness should be suspected in multitransfused patients not showing expected increment in platelet counts and thoroughly investigated to frame further guidelines in order to ensure proper management of these kind of patients.

Mesenchymal stem or stromal cells: a review of clinical applications and manufacturing practices.

Mesenchymal stem cells (MSCs) have recently generated great interest in the fields of regenerative medicine and immunotherapy due to their unique biologic properties. In this review we attempt to provide an overview of the current clinical status of MSC therapy, primarily focusing on immunomodulatory and regenerative or tissue repair applications of MSCs. In addition, current manufacturing is reviewed with attention to variation in practices (e.g., starting material, approach to culture and product testing). There is considerable variation among the 218 clinical trials assessed here; variations include proposed mechanisms of action, optimal dosing strategy, and route of administration. To ensure the greatest likelihood of success in clinical trials as the field progresses, attention must be given to the optimization of MSC culture.

Serial assessment of biochemical changes in irradiated red blood cells.

BACKGROUND: Transfusion associated graft vs host disease (TA-GVHD) is delayed effect of blood component therapy with a very high mortality rate. The use of irradiated blood components is the only proven method to prevent TA-GVHD in susceptible patients. AIM: Our study was designed to analyze the quality of irradiated PRBCs in terms of their biochemical parameters during a storage period up to 28 days post irradiation. METHODS: A total of 80 PRBC units were analyzed, 40 units each stored in CPDA-1 and additive solution-SAGM. The units were evaluated serially for the following biochemical parameters, plasma/ supernatant potassium, sodium, pH, glucose, lactate, plasma/supernatant hemoglobin and red cell ATP. We further evaluated the differences in these parameters between units irradiated on day 1 and day 7 of storage and stored these units up to 28 days and 35 days respectively. Ten units in each group were used as control. The assessment was done at weekly intervals from the day of irradiation. RESULTS: Within each group of red cells, there was a rise in mean concentration of plasma potassium (K(+)) from day 1 to last day of storage. There was a highly significant difference (P<0.01) between irradiated and control units after first week of storage in both types of PRBCs. Irradiated CPDA-1 PRBC had significantly higher (K(+)) than irradiated SAGM PRBC. Intergroup comparison revealed significantly higher (P<0.05) mean hemoglobin in irradiated CPDA-1 PRBC as compared to SAGM PRBC. The mean pH was significantly higher (P<0.05) in irradiated CPDA-1 PRBC as compared to irradiated SAGM PRBC only on day 7 of storage. ATP levels significantly decreased in irradiated units as compared to control units. SAGM PRBCs had significantly higher (P<0.05) mean ATP concentration than CPDA-1PRBCs. CONCLUSION: Our study demonstrates that SAGM-PRBCs show better stability after irradiation compared to CPDA-1 PRBCs. The limits of safety for CPDA-1 PRBCs appear to be two weeks after irradiation. SAGM-PRBCs on the other hand show acceptable limits of safety up to three weeks of irradiation. The shelf life of irradiated PRBCs may vary depending upon the storage solution and day of irradiation.