Hematopoietic stem-cell transplantation in a zoo of multidrug-resistant organisms: Data from a cancer center in eastern India.

BACKGROUND: Infections by multidrug-resistant organisms (MDRO) are a major hurdle in hematopoietic stem-cell transplants (HSCTs). Conditioning regimens lead to mucosal barrier injury, which in-turn leads to transmigration of gut bacteria and sepsis. Pre-transplant stool and throat surveillance cultures can guide empirical antibiotic policy during the neutropenic period. In this paper, we document colonization with MDRO in pre-transplant surveillance cultures and the correlation with bloodstream infections in HSCT patients and analyze transplant outcomes with respect to these infections. METHODS: A single-center, retrospective study on HSCT was performed between January 2021 and December 2021. The incidence of bacterial infections, percentage of MDROs, correlation with pre-transplant stool/throat surveillance cultures, and their impact on overall 100-day and post-100-day to 6-month post-transplant survival were analyzed. RESULTS: Sixty-four patients were included in the study. Pre-transplant stool surveillance cultures were positive for MDRO in 85.9% of patients. Almost half (48.5%) of the isolates were positive for carbapenemase-producing genes (mainly New Delhi metallo-beta-lactamase-1 [NDM-1] and oxacillinase-48 [OXA-48]). Eighteen patients (18/64, 28%) had a positive blood culture for MDRO in the peri-engraftment neutropenic period. Correlation between surveillance and blood cultures was seen in 61% (11/18) of patients. All-cause mortality was 14.1% (9/64) and 25% (16/64) in patients at 100 days and 6 months post-HSCT, respectively. The 100-day and post-100-day all-cause mortality rates were higher in patients with Gram-negative MDRO bloodstream infections (p < .012 and <.008, respectively). CONCLUSION: MDRO infections can adversely affect HSCT outcomes. Pre-transplant stool and throat surveillance cultures may guide empirical antibiotic policy and lead to favorable transplant outcomes.

Precursor B-cell acute lymphoblastic leukaemia-a global view.

As haematologists, we always seek to follow standardised guidelines for practice and apply the best treatment within our means for our patients with blood diseases. However, treatment can never follow an exact recipe. Opinions differ as to the best approach; sometimes more than one treatment approach results in identical outcomes, or treatments differ only by the manner in which they fail. Furthermore, the haematologist is faced with constraints relating to the local economic environment. Patients too are not the same the world over. Early presentation is commoner in the developed world, as is the patient's understanding of the disease process. This in turn has an impact on the way patients are managed, the rigorousness of patient adhesion to the treatment schedule and the outcome. Here we take a look at the precursor B-cell acute lymphoblastic leukaemia in an adolescent in a range of different settings from low- to high income countries with widely differing challenges for diagnosis, therpy and follow-up. For these reasons, given the same starting conditions, patients will be treated differently according to the institute and the country they are in. Experts from around the world have been tasked to describe their management plan and rationale for a specific disease presentation. Here they explore the management of precursor B-cell acute lymphoblastic leukaemia (pre-B ALL) in five different institutions worldwide with a focus on those with more or less strained economies. We end with a conclusion from an expert in the field comparing and contrasting these different management styles and considering their merits and limitations.

Clinical and laboratory profile of anti-M.

CONCLUSIONS: Anti-M is a frequently detected naturally occurring antibody that has been reported in various clinical settings and also in voluntary donors. We describe here the clinical and laboratory findings of 11 cases with anti-M detected at our center. This report is a retrospective study in which we reviewed our immunohematology laboratory records for cases involving anti-M. Both donor and patient data from a 28-month period (September 2014 to December 2016) were reviewed. During this period, 11 examples of anti-M were detected (8 patients, 1 voluntary whole blood donor, and 1 hematopoietic stem cell donor. Anti-M was also detected in one external quality assessment scheme sample received during this period. In conclusion, anti-M can be detected in various clinical settings. This antibody can be clinically significant; in the laboratory, it can present as a serologic problem such as an ABO group discrepancy or an incompatible crossmatch. After detection, management and course of action is determined by both the antibody characteristics and the clinical setting.

An analysis of transfusion support in haematopoietic stem cell transplantation--report from a centre in India.

BACKGROUND: Transfusion support in haematopoietic stem cell transplantation (HSCT) can be very demanding and challenging. The conditioning regimen, stem cell dose, donor type, presence of GvHD, infection all influence transfusion therapy in haematopoietic stem cell transplantation (HSCT). We retrospectively analysed the first 100 days transfusion requirements among HSCT recipients with haematological as well as non-haematological malignancies in our centre. MATERIALS AND METHODS: Transfusion data were retrieved for 100 patients who had undergone HSCT over a period of two years. The HSCT recipients were divided into three groups: autologous, allogenic and haplo-identical. Allogenic group was subdivided into matched related donor (MRD) and matched unrelated donor (MUD). The allo and haplo groups were then classified on the basis of the ABO compatibility as major, minor, bi-directional and compatible. We analysed the mean requirement of blood components (RBC, RDP, SDP and FFP) within the first 100 days of HSCT in each category. RESULTS AND DISCUSSION: Haematologic malignancies constituted 97% of the indications for HSCT. Allo-HSCT constituted 50% of the HSCT, of which 92% were MRD. Auto and haplo-HSCT constituted 40% and 10% respectively. Mean requirement for all products--RBC, SDP, RDP and FFP--was highest in the haplo category, followed by the allo category and then the auto HSCT category. The mean product requirement in the MUD category was significantly higher than in the MRD category (p < 0.05). The mean product requirement in the major and bidirectional ABO incompatible group was significantly higher as compared to the minor and ABO compatible group (p < 0.05). Hence our data may help transfusion medicine specialists to understand the transfusion requirement in stem cell transplant settings from developing countries like India. The average number of blood donors required for each group of stem cell transplant patients can also be roughly predicted from this study.

Immunosuppressive Therapy and Bone Marrow Transplantation for Aplastic Anaemia--The CMC Experience.

This is a single centre experience on the use of immunosuppressive therapy (IST) and stem cell transplantation (SCT) in patients with aplastic anaemia. Between 1985 and December 2013, 530 patients underwent IST while 214 underwent allogeneic SCT. Overall response rate with the use of IST was 58% with higher responses seen in adults (65.1%) compared to children (35.8%) [p = 0.001]. At a median follow up of 34 months (range: 1 - 264), 5 year KM estimates for OS for the entire group is 68.2 ± 2.2%. Loss of response or relapse was seen in 27 responders while clonal evolution to PNH was seen in 8 patients and transformation to MDS or AML was seen in 3. The 5 yr OS for children (45.7 ± 4.7%) was significantly lower than the OS of age groups 16-30 (75.6 ± 3.6%), 31-50 years (76.2 ± 4.2%) and > 50 years (73.0 ±4.2%) (p = 0.0001). SCT was performed in 214 patients with engraftment seen in 91%. The incidence of grade II-IV acute graft versus host disease (GVHD) was 38.4% with grade III-IV GVHD in 11.7%. Chronic GVHD was seen in 47.5% of evaluable patients with majority (73%) being limited chronic GVHD. At a median follow up of 32 months (range: 1 - 244), the 5 year KM estimates of OS for the entire cohort is 64.8 ± 3.3%); The 5 yr OS was significantly higher with the use of Flu/Cy (5 yr OS of 73.8 ± 3.6%) compared to Cy/ATG (5 yr OS of 44.4 ± 9.6%) or Flu/Bu conditioning (5 yr OS of 52.4 ± 8.9%) [p = 0.001]. Imp: SCT and IST offer good response rates and survival in Indian patients with AA except in children receiving IST.

Cancer research in India: national priorities, global results.

Over the past 20 years, cancer research in India has grown in size and impact. Clinicians, scientists, and government and state policy makers in India have championed cancer research, from studies to achieve low-tech, large-scale health outcomes to some of the most advanced areas of fundamental cancer science. In this paper, we frame public policy discussions about cancer with use of an in-depth analysis of research publications from India. Cancer research in India is a complex environment that needs to balance public policy across many competing agendas. We identify major needs across these environments such as those for increased research capacity and training and protected time for clinical researchers; for more support from states and enhanced collaborative funding programmes from government; for development of national infrastructures across a range of domains (ie, clinical trials, tissue banking, registries, etc); and for a streamlined and rational regulatory environment. We also discuss improvements that should be made to translate research into improvements in cancer outcomes and public health.

Role of minimal residual disease monitoring in acute promyelocytic leukemia treated with arsenic trioxide in frontline therapy.

Data on minimal residual disease (MRD) monitoring in acute promyelocytic leukemia (APL) are available only in the context of conventional all-trans retinoic acid plus chemotherapy regimens. It is recognized that the kinetics of leukemia clearance is different with the use of arsenic trioxide (ATO) in the treatment of APL. We undertook a prospective peripheral blood RT-PCR-based MRD monitoring study on patients with APL treated with a single agent ATO regimen. A total of 151 patients were enrolled in this study. A positive RT-PCR reading at the end of induction therapy was significantly associated on a multivariate analysis with an increased risk of relapse (relative risk = 4.9; P = .034). None of the good risk patients who were RT-PCR negative at the end of induction relapsed. The majority of the relapses (91%) happened within 3 years of completion of treatment. After achievement of molecular remission, the current MRD monitoring strategy was able to predict relapse in 60% of cases with an overall sensitivity and specificity of 60% and 93.2%, respectively. High-risk group patients and those that remain RT-PCR positive at the end of induction are likely to benefit from serial MRD monitoring by RT-PCR for a period of 3 years from completion of therapy.

Identification of rare and novel deletions that cause (뫧)0-thalassaemia and hereditary persistence of foetal haemoglobin in Indian population.

OBJECTIVES: Hereditary persistence of foetal haemoglobin (HPFH) and (δß)(0) -thalassaemia are conditions caused by large deletions that involve δ- and ß-globin genes in the ß-globin cluster, and they are characterized by increased haemoglobin (HbF) levels in adults. Significant phenotypic diversity is observed between the different mutations that cause these conditions. Molecular characterization of these deletions is important for accurate molecular diagnosis, and they will also provide the information on the cis-acting genetic regulatory elements present in the ß-globin cluster. METHODS: We performed gap-PCR, multiplex ligation-dependent probe amplification (MLPA), quantitative fluorescent multiplex PCR (QF-MPCR) and DNA sequencing to detect and characterize the deletions in the ß-globin cluster. RESULTS: We characterized six different deletions resulting in (δß)(0) -thalassaemia or HPFH in 51 unrelated families. CONCLUSION: With the help of multiple genetic tools, we performed comprehensive genetic analysis of HPFH and (δß)(0) -thalassaemia in Indian population and could define the molecular basis of these conditions in this population. We also identified two novel HPFH mutations, 49.98 kb (HPFH-9) and 86.7 kb (HPFH-10) deletions, in this population.

Jumping translocation in a case of de novo infant acute myeloid leukemia.

An infant presented with fever and purulent discharge from the left ear, proptosis of the right eye, and hepatosplenomegaly. She was diagnosed with acute monoblastic leukemia on morphological and flowcytometric analysis of the bone marrow. Karyotyping showed a jumping translocation (JT) involving the long arm of chromosome 1 as the sole cytogenetic abnormality in 29 metaphases. The patient died within 2 months of diagnosis. The presence of JT in a de novo infant AML as a sole cytogenetic abnormality indicates its possible role in leukemogenesis unlike previous reports that have implicated its role in tumor progression only.

Novel t(2;12)(q31;p13) in a case of pediatric T-cell acute lymphoblastic leukemia.

BACKGROUND: The role of ETV6 in B-cell acute lymphoblastic leukemia (ALL) has been extensively studied, whereas only rare cases of ETV6 involvement in pediatric T-cell ALL have been described. OBSERVATION: We report a case of T-cell ALL in a 13-year-old boy with t(2;12)(q31;p13) involving ETV6, resulting in the relocation of the ETV6 from 12p13 to 2q31 locus that harbors the class 1 homeobox gene (HOX) cluster D, which is expressed during the early stages of T-cell development. CONCLUSIONS: We report a novel translocation in T-cell ALL highlighting the involvement of ETV6 and potentially the HOXD gene cluster in a case of T-cell ALL.

Melphalan-associated encephalopathy following autologous stem cell transplant: a transplanter's nightmare!

Melphalan-induced encephalopathy is a rare complication observed in patients undergoing autologous stem cell transplantation (ASCT) and is characterized by symptoms ranging from drowsiness to seizures. Previous reports have described similar cases, including a review of a large cohort of patients in whom melphalan-associated encephalopathy was identified in 2% of the patients undergoing ASCT. We describe the case of a 63-year-old male with Multiple Myeloma and underlying chronic kidney disease (CKD) who underwent ASCT with a reduced dose of melphalan due to renal dysfunction in complete remission following induction therapy and subsequent neurological deterioration, which necessitated an extensive evaluation of several neurological and infective etiologies. In this report, we highlight that melphalan-associated encephalopathy is a distinct entity complicating ASCT in patients with myeloma, especially in those with preexisting renal insufficiency, and consider its management.

Strategies to decrease inequalities in cancer therapeutics, care and prevention: Proceedings on a conference organized by the Pontifical Academy of Sciences and the European Academy of Cancer Sciences, Vatican City, February 23-24, 2023.

Analyses of inequalities related to prevention and cancer therapeutics/care show disparities between countries with different economic standing, and within countries with high Gross Domestic Product. The development of basic technological and biological research provides clinical and prevention opportunities that make their implementation into healthcare systems more complex, mainly due to the growth of Personalized/Precision Cancer Medicine (PCM). Initiatives like the USA-Cancer Moonshot and the EU-Mission on Cancer and Europe's Beating Cancer Plan are initiated to boost cancer prevention and therapeutics/care innovation and to mitigate present inequalities. The conference organized by the Pontifical Academy of Sciences in collaboration with the European Academy of Cancer Sciences discussed the inequality problem, dependent on the economic status of a country, the increasing demands for infrastructure supportive of innovative research and its implementation in healthcare and prevention programs. Establishing translational research defined as a coherent cancer research continuum is still a challenge. Research has to cover the entire continuum from basic to outcomes research for clinical and prevention modalities. Comprehensive Cancer Centres (CCCs) are of critical importance for integrating research innovations to preclinical and clinical research, as for ensuring state-of-the-art patient care within healthcare systems. International collaborative networks between CCCs are necessary to reach the critical mass of infrastructures and patients for PCM research, and for introducing prevention modalities and new treatments effectively. Outcomes and health economics research are required to assess the cost-effectiveness of new interventions, currently a missing element in the research portfolio. Data sharing and critical mass are essential for innovative research to develop PCM. Despite advances in cancer research, cancer incidence and prevalence is growing. Making cancer research infrastructures accessible for all patients, considering the increasing inequalities, requires science policy actions incentivizing research aimed at prevention and cancer therapeutics/care with an increased focus on patients' needs and cost-effective healthcare.

HLA-matched sibling bone marrow transplantation for ß-thalassemia major.

We describe outcomes after human leukocyte antigen-matched sibling bone marrow transplantation (BMT) for 179 patients with ß-thalassemia major. The median age at transplantation was 7 years and the median follow-up was 6 years. The distribution of Pesaro risk class I, II, and III categories was 2%, 42%, and 36%, respectively. The day 30 cumulative incidence of neutrophil recovery and day 100 platelet recovery were 90% and 86%, respectively. Seventeen patients had graft failure, which was fatal in 11. Six of 9 patients with graft failure are alive after a second transplantation. The day 100 probability of acute graft-versus-host disease and 5-year probability of chronic graft-versus-host disease was 38% and 13%, respectively. The 5-year probabilities of overall- and disease-free survival were 91% and 88%, respectively, for patients with Pesaro risk class II, and 64% and 62%, respectively, for Pesaro risk class III. In multivariate analysis, mortality risks were higher in patients 7 years of age and older and those with hepatomegaly before BMT. The leading causes of death were interstitial pneumonitis (n = 7), hemorrhage (n = 8), and veno-occlusive disease (n = 6). Proceeding to BMT in children younger than 7 years before development of end-organ damage, particularly in the liver, should improve results after BMT for ß-thalassemia major.

The use of a fludarabine-based conditioning regimen in patients with severe aplastic anemia--a retrospective analysis from three Indian centers.

Between 2001 and 2009, 121 patients with severe aplastic anemia (SAA) underwent hematopoietic stem cell transplantation (HSCT) using a conditioning protocol of fludarabine and cyclophosphamide at three Indian hospitals. Donors were HLA-identical sibling or family donors. Seventy-six patients were considered "high risk" as per criteria. The graft source included peripheral blood stem cells in 109 and G-CSF-stimulated bone marrow in 12. GVHD prophylaxis consisted of cyclosporine and mini-methotrexate. Engraftment occurred in 117 (96.6%) while two had graft failure and two expired in the first two wk. Neutrophil engraftment was seen at 12.3 d (range: 9-19) while platelet engraftment occurred at 12.4 d (range: 8-32). Grade II-IV acute GVHD was seen in 26.7% and grade IV GVHD in 8.6%. Chronic GVHD occurred in 44% and was extensive in 10%. The five-yr overall survival for the entire cohort is 75.8 ± 3.9% with a survival of 95.6 ± 3.1% in the low-risk group (n = 45) and 64.0 ± 5.6% in the high-risk group (n = 76). Conditioning with fludarabine and cyclophosphamide is associated with very good long-term survival in patients undergoing HSCT for SAA.

A rapid & sensitive liquid chromatography- tandem mass spectrometry method for the quantitation of busulfan levels in plasma & application for routine therapeutic monitoring in haematopoietic stem cell transplantation.

BACKGROUND & OBJECTIVES: Busulfan (Bu) in combination with cyclophosphamide is widely used in myeloablative conditioning regimen prior to haematopoietic stem cell transplantation (HSCT). Its narrow therapeutic range and toxic side effects at high systemic exposure and graft rejection at low exposure emphasize the need for busulfan dose optimization using targeted dose adjustment prior to HSCT. We report here a rapid and sensitive method to quantitate busulfan plasma levels in patients receiving busulfan as part of pre-transplant conditioning. METHODS: The method involves simple protein precipitation of the plasma followed by analysis using a high performance liquid chromatography (HPLC) with tandem mass spectrometry - electrospray ionization technique (LC-ESI MS/MS) in positive ionization mode and quantified using multiple reaction monitoring (MRM). Deuterated busulfan (d8-busulf`an) was used as the internal standard. RESULTS: The method was linear for the concentration ranging from 0 to 4000 ng/ml of busulfan with a limit of detection of 2 ng/ml and limit of quantitation of 5 ng/ml. The assay was accurate for serial concentrations of Bu in plasma for five consecutive days and the CV was less than 10 per cent. CONCLUSION: Using this rapid and sensitive method, busulfan levels were targeted and subsequent doses adjusted at our center in 26 patients receiving high dose busulfan in combination with cyclophosphamide or fludarabine.

Bortezomib-based induction therapy followed by autologous hematopoietic cell transplantation in newly diagnosed multiple myeloma patients: A single-center experience and review of Indian literature.

INTRODUCTION: High-dose chemotherapy with melphalan, followed by autologous hematopoietic stem cell transplantation (AHCT) remains the standard of care for consolidation therapy of fit patients with newly diagnosed multiple myeloma (NDMM), for more than 20 years now. MATERIAL AND METHODS: This is a retrospective study of NDMM patients who underwent AHCT at our center from 2011 to 2018. Data was undertaken using the hospital electronic medical records (EMR). RESULTS: Among transplant eligible patients (which were 764), 78 patients (10.2%) underwent AHCT. The predominant stage in the study cohort was International Scoring System (ISS)-III (55%), and IgG-kappa (44%) was the commonest subtype of multiple myeloma (MM). Light chain myeloma was found in 23.5% of patients. Pretransplant, 42%, 48%, and 10% patients were in more than very good partial response (>VGPR), very good partial response (VGPR), and partial response (PR), respectively. The median duration of follow-up was 57.2 months (range: 12.1-120.2 months). The entire cohort's 5-year overall survival (OS) and progression-free survival (PFS) were 89.1% and 41.8%, respectively. CONCLUSION: Bortezomib based triplet induction regimens were effective and well tolerated in this retrospective analysis of Indian patients. We observed that AHCT effectively achieves deep and durable remission in MM.

Molecular epidemiology of SARS-CoV-2 in healthcare workers and identification of viral genomic correlates of transmissibility and vaccine break through infection: A retrospective observational study from a cancer hospital in eastern India.

PURPOSE: Despite COVID vaccination with ChAdOx1 ncov-19 (COVISHIELD®) (ChAdOx1 ncov-19) a large number of healthcare workers (HCWs) were getting infected in wave-2 of the pandemic in a cancer hospital of India. It was important therefore to determine the genotypes responsible for vaccine breakthrough infections. METHODS & OBJECTIVES: Retrospective observational study of HCWs. Whole genome sequencing of SARS CoV-2 using Illumina NovaSeq was done. Mutations from both waves were compared to identify genomic correlates of transmissibility and vaccine breakthrough infections. RESULTS: Vaccine breakthrough infections were seen in 127 HCWs out of 1806 fully vaccinated staff (7.03%). Median number of HCWs infected per day in wave-1 was 0.92 versus 3.25 in wave-2. Majority of wave-1 samples belonged to B.1 and B.1.1 lineage. Variant of concern- Delta variant (90%), and variant of interest- Kappa variant (10%), was seen in only wave-2 samples. Total mutation observed in wave-2 samples (median â€‹= â€‹44) was 1.8 times than wave-1 sample (median â€‹= â€‹24). Spike protein in wave-2 samples had 13 non-synonymous mutation as compared to 8 seen in wave-1 samples. E484Q-vaccine escape mutant was detected in five samples of wave-2; T478K - highly infectious mutation was seen in 31 samples of wave-2. We identified a novelcoding disruptive in-frame deletion (c.467_472delAGTTCA, p. Glu156_Arg158delinsGly) in the Spike protein. This mutation was seen only in wave-2 (78%, n â€‹= â€‹39) samples. CONCLUSION: The circulating virus strains in wave-2 infections demonstrated a greater degree of infectivity. There was a significant change in the genotypes observed in wave-1 and wave-2 infections along with almost twice the number of mutations. We noted that vaccine breakthrough infections (although mostly mild).

Multi-drug resistant (MDR) and extensively drug-resistant (XDR) bacteraemia rates among cancer patients in an oncology hospital in eastern India: an 11-year retrospective observational study.

Background: Trend analysis of bacteraemias caused by multi-drug resistant (MDR) and extensively drug resistant (XDR) bacteria helps to assess efficacy of infection prevention and control (IPC) practices. Data on the trends of MDR and XDR bacteraemias are lacking from cancer patients in India. Aims: To report antibiotic resistance rates over time in bacteraemias and to assess the effect of IPC practices where patient isolation facilities were limited on the rates and trends of MDR and XDR bacteraemias from a cancer centre in eastern India. Methods: A retrospective observational study was conducted in a specialist cancer hospital in India from 2011 to 2021. The study included both patients with haematological and solid organ malignancy. Data on blood cultures and surveillance culture samples were analysed. Blood cultures were processed using BACT/ALERT® (bioMérieux, Marcy-l'Étoile, France) and the identification and antibiotic susceptibilities of bacteria were performed using VITEK® 2 (bioMérieux, Marcy-l'Étoile, France). Surveillance cultures for MDR/XDR bacteria were performed on a subset of patients and processed based on a modified method described previously. Findings: 3rd-generation cephalosporin-resistant Gram negative bacilli were the commonest cause of MDR bacteraemia (57.6%) followed by carbapenem resistant organisms (CRO) (35.7%). Bacteraemias caused by vancomycin-resistant enterococci (VRE), meticillin-resistant Staphylococcus aureus (MRSA) and colistin-resistant Gram negative bacilli were responsible for 1.3%, 2.3% and 3.0% of laboratory confirmed bloodstream infections (BSI) respectively. The ranges of the rates of MDR/XDR BSI per 1000 in-patients during the study period were: MRSA (1-1.18), VRE (0-0.88), 3rd generation cephalosporin-resistant Gram negative bacilli (10.10-20.32), CRO (5.05-13.07) and colistin-resistant Gram negative bacilli (E. coli, Klebsiella, Pseudomonas aeruginosa, Acinetobacter spp (0-1.3). Surveillance cultures collected from a subset of patients showed ranges of MRSA detection in 0-2.11%, VRE in 1.67%-7.49%, 3rd generation cephalosporin-resistant Gram negative bacilli in 55%-89.91% and carbapenem resistant Gram negative bacilli in 18.33%-31.11% of patients. Conclusion: This is one of few studies providing trend data for MDR/XDR bacteraemia rates among cancer patients in India over a decade. In a high prevalence setting it was possible to keep the rates of MDR/XDR bacteraemia controlled with IPC strategies and without adequate isolation facilities. The results are of potential interest to policy makers, IPC specialists and clinicians.

Polymorphisms in the immunoregulatory genes are associated with hematopoietic recovery and increased susceptibility to bacterial infections in patients with thalassaemia major undergoing matched related hematopoietic stem cell transplantation.

In this study, the impact of polymorphisms in the genes of proinflammatory (IL-ß, TNF-α, IL-6, IFN-γ), anti-inflammatory (transforming growth factor [TGF]-ß, IL-10, IL-Ra), and other immunoregulatory factors (FcγRIIa, NOS3) along with the conventional risk factors on the rate of hematopoietic recovery and first episodes of bacterial, viral, or invasive fungal infections in 102 patients with ß-thalassaemia major who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with relatively uniform protocols at our center from June 1995 to June 2004 with a minimum follow-up of at least 2 years were studied retrospectively for 180 days after hematopoietic stem cell transplantation (HSCT). Our data show that (1) donor IL-1RN∗2/2 (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.17-5.09; P = .018) and FCγRIIA +4481G/G genotypes (HR, 3.1; 95% CI, 1.56-6.31; P = .001) increased the incidence of bacterial infection; (2) fungal infection was increased in recipients with whose donors had IFN-γ +874T/T genotype (HR, 3.8; 95% CI, 1.08-13.62; P = .037); (3) time to neutrophil recovery was shorter in splenectomized patients (HR, 3.1; 95% CI, 1.70-5.64; P < .001), donors without IL-10 -1082A, -819T, and -592A haplotype (HR, 1.6; 95% CI, 1.02-2.39; P = .039), and recipients with IFN-γ +874A/A genotype (HR, 1.6; 95% CI, 1.05-2.56; P = .029); and (4) time to platelet recovery was shorter in patients with IL-10 -1082A/A genotype (HR, 1.8; 95% CI, 1.14-2.68; P = .010) and with donors having TNF-α -308G/G genotypes (HR, 1.8; 95% CI, 1.06-2.93; P = .028). These data suggest that outcome after allogeneic stem cell transplantation could be affected by many factors. The mechanisms by which they bring about such impact needs further evaluation.

International reporting scale of BCR-ABL1 fusion transcript in chronic myeloid leukemia: first report from India.

Achieving a major molecular response (MMR) is an important predictor of progression-free survival in chronic myeloid leukemia patients treated with imatinib. This requires accurate measurement of BCR-ABL1 transcripts normalized to a control gene, as well as defining a level (BCR-ABL1/control gene ratio) that will correlate with sustained clinical response. To make these measurements comparable between laboratories, an international scale (IS) is necessary. A BCR-ABL1/control gene ratio of 0.10% represents MMR in the IS. In collaboration with an international reference laboratory in Adelaide, S.A., Australia, we have established and validated a lab-specific conversion factor for expressing BCR-ABL1 transcript levels in the IS. In this report, we explain the process and steps involved in obtaining a valid lab-specific conversion factor for expressing BCR-ABL1 transcript levels in the IS.