Why Are Patients Not Getting a Graft? An Intent-to-Transplant Analysis in the Times of Universal Coverage and Haploidentical Donors

Introduction: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative option for patients with hematologic diseases. When considered candidates, patients face barriers to receive a transplant. Therefore, we aimed to analyze factors that limit or favor access to an alloHSCT in a population that has been HLA typed and therefore with a potential intent-to-transplant. Method(s): We retrospectively reviewed records from 2015 until the start of the COVID19 pandemic in two Mexican government- funded transplant centers and one private that have in-house HLA typing;in two of them, an outpatient transplant strategy is followed for most patients. HLA-typed patients who were potentially eligible for transplantation were included and their outcomes were assessed in an intent-to-transplant basis. We compared the outcomes of patients who underwent transplantation to those who did not and evaluated contributing barriers to access alloHSCT with multivariate logistic regression. Result(s): A total of n=374 patients were analyzed. The median age at HLA-typing was 35 years (IQR 23-47);59.3% had acute(Table Presented) leukemia, 17.4% bone marrow failure or myelodysplastic neoplasms, 13.1% lymphoma, 8% myeloproliferative neoplasms, 1.1% chronic lymphocytic leukemia and 1.1% multiple myeloma. Most patients (55.9%) had government insurance coverage. Median time from diagnosis to HLA-typing was 8 months (IQR 3-19). The majority had a potential donor (94.4%): 56.4% haploidentical, 37.4% a matched sibling donor and 0.5% an unrelated donor. Almost half of them received a transplant (n=185, 49.5%), the median time from HLA-typing to alloHSCT was 2 months (IQR 1-5.5). Disease activity or progression was the biggest barrier for transplantation;Table 1. Donor availability limited transplant access for 12.1% of patients. Access to transplantation was favored by private/out-of-pocket payment (OR 2.1 95% CI 1.3-3.4), and receiving care in the outpatient center (OR 6.4 95% CI 4-10.0), while HLA matching was not (OR 1.2 95% CI 0.8-1.8). Non-relapse mortality in alloHSCT was 21%. Median overall survival (OS) from the intent-to-transplant cohort was 16 months (CI 95% 12.4-19.6). An OS landmark analysis for patients alive at or beyond 2 months (the median time from HLA-typing to alloHSCT) showed prolonged survival in alloHSCT (30 vs 12 months, p <.001), Figure 1. By the time of the analysis 159 patients (42.5%) were still alive and 115 (30.7%) were event-free.(Figure Presented)Conclusion: The most frequent barrier to transplantation was the disease itself, followed by the transplant waitlist and comorbidities. Access to resources and an outpatient strategy or "center effect" favored alloHSCT. In the era of haploidentical transplantation, donor availability was a smaller issue. Efforts to improve timely referrals and access to effective pre-transplant therapies should be undertaken.Copyright © 2023 American Society for Transplantation and Cellular Therapy

The Leukoreductive Power of Vinblastine in Acute Myeloid Leukemia with Hyperleukocytosis: A Pilot Study

Introduction Acute myeloid leukemia (AML) with hyperleukocytosis is associated to high early mortality rates and needs aggressive treatment. Induction chemotherapy (ICH), leukapheresis and hydroxyurea (HU) are the most frequent used leukoreductive strategies. Delay in ICH is very common, leukapheresis is not widely available and hydroxyurea and leukapheresis do not modify early mortality rates. Therefore alternative strategies to leukoreduce patients with AML and hyperleukocytosis are needed. Vinblastine is widely available, cheap, with preclinical activity and promising results in relapsed AML. We explored the leukoreductive power of a single dose of vinblastine in patients with newly diagnosed AML and hyperleukocytosis. Patients and methods We conducted a prospective pilot study that included consecutive patients with newly diagnosed non-M3 AML, aged 16 to 60 years, and with a WBC ≥50,000/µL at time of presentation and in whom immediate ICH with 7+3 was not possible because of hospital limitations (i.e. delay in ICH drug availability). We excluded patients with PML/RAR-alfa rearrangement and/or t(15;17), poor performance status (ECOG >2), any preceding chemotherapy, organic dysfunction (defined as a modified Marshall score ≥2) or pregnancy. After diagnostic confirmation, a single dose of vinblastine at 6 mg/m2 i.v. was administered. We documented leukocytes (WBC) and number of blasts on the day of vinblastine administration (0h) and 48 hours later. We represented the achieved leukoreduction with boxplots and compared the absolute reduction in WBC (delta WBC) and blasts (delta blasts) after vinblastine administration. We compared the leukoreductive power of vinblastine to other leukoreductive strategies (HU, leukapheresis). We calculated toxicities (grade 4 neutropenia and thrombocytopenia), median length of hospitalization and parental antibiotics, and overall survival (OS). We documented cases of disseminated intravascular coagulation, leukostasis and tumor lysis syndrome. This study complies with the Declaration of Helsinki, and our local ethics committee. Results A total of 11 patients were enrolled in the study, seven were men (63.6%), with a median age of 48 (21-78) years. Median follow-up was 21 days (2-833 days). The most frequent morphologic subtype was M4 (3, 27.3%), M5 (2, 18.2%) and M2 (2, 18.2%). Cytogenetics were obtained in three cases (27.3%) and all of them were classified as intermediate risk. Forty eight hours after vinblastine administration the WBC lowered from 122x109/L (50.1-380) to 47.3x109/L (22.1-170) representing a 54% (26.7-84.2) decrese (p=0.0001) (figure 1) while blasts number lowered from 204 x 109/L (47.8-361) to 6.4 x 109/L (0-1.6) representing a 85.7% (75-100) decrease (p=0.005) (figure 1). In Table 1 we compare our results with other strategies. All patients experienced grade 4 neutropenia and thrombocytopenia. There were no cases of disseminated intravascular coagulation, leukostasis or tumor lysis syndrome. Severe infections (grade III-IV) occurred in 8 patients (two patients presented neutropenic colitis, five with severe pneumonia, and one SARS-COV2). Four patients presented septic shock and died during induction therapy. Median length of hospitalization and parental antibiotics were 19 days (2-30) and 7 days (range, 2-24), respectively. A CR was achieved in 4 patients (36.4%) after one induction cycle. One patient presented refractory disease and five died before response evaluation. One patient relapsed at 16 months of follow-up. Median OS was 11 months (0-31.8). Allogeneic stem cell transplantation was performed in 1 patient. Conclusion We documented a marked reduction in both WBC and blasts after 48 hours of vinblastine administration. Our study suggests that the leukoreductive power of a single dose of vinblastine is similar to HU and leukapheresis in patients with AML with hyperleukocytosis. Vinblastine is a widely available, cheap and myelotoxic drug that could extend the arsenal to treat newly diagnosed AML with hyperleukocytosis. [Formula presented] Disclosures: Gomez-Almaguer:AstraZeneca:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Roche:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Pfizer:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Celgene/BMS:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Amgen:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AbbVie:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Hematopoietic stem cell transplantation (HSCT) in the COVID-19 pandemic era

The pandemic of coronavirus infectious disease-2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a threat to global health. This has become an obstacle for the practice of hematology, mostly in low-middle income countries. For those hematologist and oncologists who perform hematopoietic stem cell transplantation HSCT the usual challenges of this kind of medical procedures have increased because of the COVID-19 pandemic. The importance of find the best route for performing HSCT avoiding excessive COVID-19 risk is of great importance. By doing so, we have been able to conduct 170 hematopoieic stem cell transplants during the COVID-19 pandemia.

Aplastic anemia

Medical practice in general has changed due to coronavirus disease 2019 (COVID-19) pandemic. Some hematologic diseases require immunosuppresive therapy placing patients at high risk of infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Aplastic anemia (AA) especially the very severe type in which the count of absolute neutrophils is less than 200/mu l is a life-threatening condition. Although bone marrow transplant is a potential curative treatment, it should be delayed temporally in order to prevent a contagion. Hospitalization may expose patients to infection, thus an ambulatory immunosuppression with oral cyclosporine and thrombopoietin agonist should be an adequate option. This work reviews international and national treatment recommendations and follow-up of patients with AA based on experiences from countries that have already faced this health emergency.