Blood Reviews最新文献

We report 634 patients who underwent unmanipulated haploidentical (HAPLO) bone marrow transplantation (BMT) in two Centers. The diagnosis was acute myeloid leukemia (AML) (n = 251), acute lymphoblastic leukemia (ALL)(n = 107), myelodysplastic syndrome and myelofibrosis (MDS + MF) (n = 125) and chronic lymphoproliferative disorders (n = 151). Median age was 52 years (16–74). Graft versus host disease (GvHD) prophylaxis was intravenous cyclosporin (CSA) starting on day 0, oral mycophenolate on day +1, and post-transplant cyclophosphamide (PTCY) on days +3 + 5. Primary graft failure was seen in 23 patients (3,6%); 17 /23 (74%) were rescued with second HAPLO graft, and were alive at one year. The cumulative incidence of acute GvHD grade II-IV was 29% and 3% for grade III-IV; the cumulative incidence of moderate severe chronic GvHD was 23%: older donor and patients age were significant predictors of both acute and chronic GvHD. The overall non relapse mortality (NRM) at 2 years was 19%: 8%, 21% and 30% in patients aged <40, 41–60 > 60 years. Disease free survival (DFS) at 5 years was 64% for acute leukemia in first remission, 51% for acute leukemia CR2, 25% for acute leukemia advanced disease and 49% for MDS/MPN.

We confirm, on a relatively large number of patients, that unmanipulated HAPLO BMT with PTCY on days +3 + 5, mostly after a myeloablative conditioning regimen, is followed by a low incidence of graft failure and grade III-IV GvHD; moderate severe chronic GvHD is 23% and NRM at 2 years 19%; 5 year DFS is influenced by remission status of the underlying disease.

Chronic lymphocytic leukemia (CLL) is a B cell neoplasm characterized by the accumulation of aberrant monoclonal B lymphocytes. CLL is the predominant type of leukemia in Western countries, accounting for 25% of cases. Although many patients remain asymptomatic, a subset may exhibit typical lymphoma symptoms, acquired immunodeficiency disorders, or autoimmune complications. Diagnosis involves blood tests showing increased lymphocytes and further examination using peripheral blood smear and flow cytometry to confirm the disease. With the significant advancements in machine learning (ML) and artificial intelligence (AI) in recent years, numerous models and algorithms have been proposed to support the diagnosis and classification of CLL. In this review, we discuss the benefits and drawbacks of recent applications of ML algorithms in the diagnosis and evaluation of patients diagnosed with CLL.

The guidelines for classification, prognostication, and response assessment of myelodysplastic syndromes/neoplasms (MDS) have all recently been updated. In this report on behalf of the International Consortium for MDS (icMDS) we summarize these developments. We first critically examine the updated World Health Organization (WHO) classification and the International Consensus Classification (ICC) of MDS. We then compare traditional and molecularly based risk MDS risk assessment tools. Lastly, we discuss limitations of criteria in measuring therapeutic benefit and highlight how the International Working Group (IWG) 2018 and 2023 response criteria addressed these deficiencies and are endorsed by the icMDS. We also address the importance of patient centered care by discussing the value of quality-of-life assessment. We hope that the reader of this review will have a better understanding of how to classify MDS, predict clinical outcomes and evaluate therapeutic outcomes.

Recent developments of assisted reproduction techniques turned possible to avoid the infertility consequences of oncologic treatments, but fertility preservation (FP) has been somewhat neglected in women with hematologic diseases undergoing gonadotoxic treatments. For these specific cases, the current options for FP include the cryopreservation of embryos, mature oocytes and ovarian tissue, and oocyte in-vitro maturation. We intend to make patients and clinicians aware of this important and relevant issue, and provide hematologists, assisted reproduction physicians and patients, with updated tools to guide decisions for FP. The physicians of the units responsible for female FP should always be available to decide on the best-individualized FP option in strict collaboration with hematologists. With a wide range of options for FP tailored to each case, a greater level of training and information is needed among clinicians, so that patients proposed to gonadotoxic treatments can be previously advised for FP techniques in hematological conditions.

Abbreviated abstract

Recent developments of assisted reproduction techniques turned possible to preserve the fertility of women with hematologic diseases undergoing gonadotoxic treatments.

Current options for fertility preservation in women with hematologic diseases are presented.

It is imperative to offer fertility preservation to all women before starting any gonadotoxic treatment and in some cases after treatment.

Fertility preservation methods enable to later achieve the desired pregnancy

In recent years, the therapeutic landscape of myeloid malignancies has been completely revolutionized by the introduction of several new drugs, targeting molecular alterations or pathways crucial for leukemia cells survival. Particularly, many agents targeting apoptosis have been investigated in both pre-clinical and clinical studies. For instance, venetoclax, a pro-apoptotic agent active on BCL-2 signaling, has been successfully used in the treatment of acute myeloid leukemia (AML). The impressive results achieved in this context have made the apoptotic pathway an attractive target also in other myeloid neoplasms, translating the experience of AML. Therefore, several drugs are now under investigation either as single or in combination strategies, due to their synergistic efficacy and capacity to overcome resistance.

In this paper, we will review the mechanisms of apoptosis and the specific drugs currently used and under investigation for the treatment of myeloid neoplasia, identifying critical research necessities for the upcoming years.

Platelet transfusion refractoriness due to HLA alloimmunization presents a significant medical problem, particularly among multiply transfused patients with hematologic malignancies and those undergoing hematopoietic stem cell transplants. HLA compatible platelet transfusions also impose significant financial burden on these patients. Recently, several novel mechanisms have been described in the development of HLA alloimmunization and platelet transfusion refractoriness. We review the history of platelet transfusions and mechanisms of HLA-sensitization and transfusion refractoriness. We also summarize advances in the diagnosis and treatment of platelet transfusion refractoriness due to HLA alloimmunization.

PTCY has been mainly used in haploidentical transplant (haploHSCT), but its use in matched donors allowed better evaluation of infectious risk conferred separately by PTCY or donor type.

PTCY increased the risk of bacterial infections, both in haploidentical and matched donors, mainly pre-engraftment bacteremias. Bacterial infections, particularly due to multidrug-resistant Gram-negatives, were main causes of infection-related deaths.

Higher rates of CMV and other viral infections were reported, mainly in haploHSCT. The role of donor might be more important than the role of PTCY. PTCY increased the risk of BK virus associated hemorrhagic cystitis, and seemed associated with higher risk of respiratory viral infections.

Fungal infections were frequent in haploHSCT PCTY cohorts without mold active prophylaxis, but the exact role of PTCY needs to be established.

Infections appear to be increased in patients receiving PTCY, although the exact role of GvHD prophylaxis and donor type can only be assessed in prospective trials.

Core binding factor acute myeloid leukemia (CBF AML), defined by t(8;21) or inv(16), is a subset of favorable risk AML. Despite its association with a high complete remission rate after induction and relatively good prognosis overall compared with other subtypes of AML, relapse risk after induction chemotherapy remains high. Optimizing treatment planning to promote recurrence free survival and increase the likelihood of survival after relapse is imperative to improving outcomes. Recent areas of research have included evaluation of the role of gemtuzumab in induction and consolidation, the relative benefit of increased cycles of high dose cytarabine in consolidation, the utility of hypomethylating agents and kinase inhibitors, and the most appropriate timing of stem cell transplant. Surveillance with measurable residual disease testing is increasingly being utilized for monitoring disease in remission, and ongoing investigation seeks to determine how to use this tool for early identification of patients who would benefit from proceeding to transplant. In this review, we outline the current therapeutic approach from diagnosis to relapse while highlighting the active areas of investigation in each stage of treatment.

High dose Post transplant cyclophosphamide (PTCy) is now regarded as a very effective way of preventing acute and chronic GvHD, and it's use has rapidly expanded world-wide.

In search of an ideal partner or alternative to conventional immunosuppressive agents, rabbit anti-thymocyte globulin (ATG) and, more recently, post-transplant cyclophosphamide (PT-Cy) have both emerged as valid and efficient options for preventing graft-versus-host disease (GvHD). To further reduce the risk of GvHD, strategies combining ATG and PT-Cy have recently been investigated. In a haploidentical setting, retrospective studies suggest that combining PT-Cy and ATG may result in a lower incidence of chronic GvHD without increasing the risks of infection or relapse, when compared to PT-Cy without ATG. In haploidentical or unrelated donor settings, adding reduced doses of PT-Cy to ATG may reduce the risk of acute and chronic GvHD and improve survival, particularly GvHD-free, relapse-free survival (GRFS), when compared to ATG without PT-Cy. Overall, the combination of PT-Cy and ATG is a safe and promising approach for patients with hematological malignancies undergoing allogeneic hematopoietic stem cell transplantation (HSCT).