Only 20–30% of patients requiring a blood and marrow transplantation (BMT) have a matched family donor. For the rest, alternative sources of graft are necessary to provide this curative procedure. ...Over the past 25 years, BMT from volunteer unrelated donors has undergone immense developments to be at par with matched family donor transplants. Similar developments have been witnessed in the field of unrelated cord blood transplantation. Thus, 90% of patients requiring a BMT in the developed worlds receive one from either of the two alternative graft sources. However, >11 million volunteer unrelated donors and 25,000 cord blood units worldwide do not solve the problem for patients from developing countries, due to lack of compatible human leukocyte antigen (HLA) match and enormous financial burden. Thus, Asian countries such as China and Korea have developed Haploidentical or mismatched family donor transplantation for their population with great success. In the light of these developments, this article discusses the options and opportunities for alternative donor BMT in the Indian scenario.
CRE is the major concern in the patients suffering from hematological malignancy but the data on the impact of colonization in such patients is scarce. We conducted a prospective surveillance study ...of CRE on 225 patients of haematological malignancies (HM), who required hospital admission between October 2013 to January 2016. The median age of the cohort was 45 years(range,2-84). The cohort included a broad representation of diseases; AML (n=58), ALL(n=44), Lymphoma (n=76), Myeloma(n=22), CML(8) and Others (n=17). Rectal swabs were taken for cultures in all patients during first day of admission and repeated subsequently on weekly basis for continuous hospital stay or in subsequent admissions.47 (21%) patients were colonized with CRE on admission. This increased to 45% on prolonged hospital stay/ contact for more than 4 weeks with 72 (32%) patients being colonized overall. The highest number of patients colonized with CRE at diagnosis was those with AML (30%). The non-relapse mortality (NRM) of the cohort at 6 months was 10.3%. This was 14% in those with acute leukemia compared to 5.8% in others (p=0.02). Furthermore, this was highest in patients with AML (22.9% vs 6.1% in others; p=0.001). CRE related events accounted for 77% of mortality. NRM was 29.6% in those colonized with CRE during hospitalization compared to 10.5% in those colonized at admission with no NRM in those not colonized with CRE (p=0.0001). Amongst patients with AML, colonization with CRE during hospitalization was associated with a NRM of 54.9%(95%CI 32.4-67.4%) compared to those colonized at admission(11.8; 95%CI 4.0-19.6) and those not colonized(0%)(p=0.0001). This trend was true for patients without AML as well (27.3% vs 10.3% vs 0%; p=0.0001). On multivariate analysis, colonization with CRE during hospitalization was the most important risk factor for NRM in patients with hematological malignancies (HR-7.1; 95%CI 3.1-16.1). Our data demonstrates that a substantial proportion of patients with HM are colonized with CRE without prior hospitalisations but those with nosocomial colonization have the highest risk of mortality, particularly in those with AML.
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No relevant conflicts of interest to declare.
The concept of reduced intensity conditioning (RIC) in allogeneic transplantation had challenged our conventional wisdom about the necessity of high-dose chemo-radiotherapy in order to achieve donor ...engraftment. The feasibility of RIC in elderly and infirm patients who would not otherwise be considered suitable for a conventional allogeneic transplantation caused a surge of interest in RIC procedures in the late 90s and early part of this decade which was however, not tempered by the balanced need for clinical trials. Although the initial expectations of reduction in graft-versus-host-disease (GVHD) were belied by the high incidences of GVHD, the importance of GVHD, particularly chronic, in controlling haematological malignancies with poor prognosis was often well exemplified. In addition, the conventional outcome measures in allogeneic transplantation such as 100- day mortality became irrelevant in the era of RIC due to reduction in early regimen-related toxicities. This did not always translate to improved overall survival due to late attritions from relapse, GVHD or late infectious complications. The enthusiasm for performing RIC in malignant diseases seems to have reached a plateau, but its true potential probably remains unexplored. In light of our current understanding of RIC, this article will highlight the future of this procedure in haematological malignancies.
Mycobacterium-w (Mw) was shown to boost adaptive natural killer (ANK) cells and protect against COVID-19 during the first wave of the pandemic. As a follow-up of the trial, 50 healthcare workers ...(HCW) who had received Mw in September 2020 and subsequently received at least one dose of ChAdOx1 nCoV-19 vaccine (Mw + ChAdOx1 group) were monitored for symptomatic COVID-19 during a major outbreak with the delta variant of SARS-CoV-2 (April–June 2021), along with 201 HCW receiving both doses of the vaccine without Mw (ChAdOx1 group). Despite 48% having received just a single dose of the vaccine in the Mw + ChAdOx1 group, only two had mild COVID-19, compared to 36 infections in the ChAdOx1 group (HR-0.46, p = 0.009). Transcriptomic studies revealed an enhanced adaptive NK cell-dependent ADCC in the Mw + ChAdOx1 group, along with downregulation of the TLR2-MYD88 pathway and concomitant attenuation of downstream inflammatory pathways. This might have resulted in robust protection during the pandemic with the delta variant.
Allogenic hematopoietic cell transplantation (HCT) is the best curative approach for patients with severe aplastic anemia (SAA). The outcomes of HCT from haploidentical family donors (HFDs) have ...improved, making it a feasible option for patients lacking an HLA-identical donor. However, data on HFD-HCT for younger patients with SAA is sparse. In this multicenter retrospective study, we evaluated the outcomes of 79 patients undergoing HFD-HCT for SAA. All the patients were heavily pretransfused, the median time to HCT was >12 months, and 67% had failed previous therapies. Conditioning was based on fludarabine (Flu)-cyclophosphamide (Cy)-antithymocyte globulin (ATG)/total body irradiation (TBI) with or without thiotepa/melphalan (TT/Mel). Post-transplantation Cy (PTCy) and calcineurin inhibitors (CNIs)/sirolimus were used as graft-versus-host disease (GVHD) prophylaxis with or without abatacept. The rate of primary graft failure (PGF) was 16.43% overall, lower in patients conditioned with TT/Mel. The incidences of acute and chronic GVHD were 26.4% and 18.9%, respectively. At a median follow-up of 48 months, the overall survival (OS) and event-free survival (EFS) were 61.6% and 58.1%, respectively. Both OS and EFS were better in the TT/Mel recipients and with abatacept as GVHD prophylaxis. On multivariate analysis, the use of abatacept was found to favorably impact the outcome variables, including GVHD and EFS. Our study suggests that PTCy-based HFD-HCT is a reasonable option for young patients with high-risk SAA, in whom optimization of conditioning and GVHD prophylaxis might further improve outcomes.
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