Intensive salvage chemotherapy with VDTPACE or mCBAD followed by hematopoietic stem-cell support for refractory/relapsed multiple myeloma.

INTRODUCTION: Triple- and quad-refractory multiple myeloma patients usually have an aggressive course and a poor prognosis. Available therapeutic options are scarce. METHODS: The objective of the current study was to evaluate responses and toxicities of VDTPACE or mCBAD with hematopoietic stem-cell support as a bridge to subsequent therapies in patients with refractory/relapsed multiple myeloma. RESULTS: Thirteen patients were included (11 mCBAD, 2 VDTPACE), and 21 cycles of chemotherapy with hematopoietic stem-cell support were delivered. Mean number of previous therapies was 4.8. Stem cells were infused on a median day 9.9 after chemotherapy. Mean time to neutrophil recovery was 18.2 days in patients receiving the first cycle and 15.9 following subsequent cycles. Before therapy, most patients were in PD (77%), PR (15%), or VGPR (8%). Following treatment, the best responses achieved were PR (46%), VGPR (46%), and CR (8%). Median overall and progression-free survivals were 17 and 9 months. There has been no case of non-relapse mortality. In the 21 cycles, the main complications were infectious. CONCLUSION: Intensive chemotherapy can decrease disease burden in patients with relapsed/refractory MM, and stem-cell support can successfully decrease toxicities and treatment-related mortality associated with these regimens and may be a good bridging option.

Costs of matched-sibling, unrelated, and haploidentical hematopoietic cell transplantation and risk factors for greater financial burden - a Brazilian FACT-accredited single-center analysis.

The complexity and costs of hematopoietic cell transplantation (HCT) have increased over the last decades with the popularization of unrelated donor (URD) transplantation and the introduction of haploidentical transplantation with posttransplant cyclophosphamide. Few studies have addressed this issue. The objective of this study was to analyze HCT costs in a single FACT-accredited private non-profit hospital. We included 79 patients who underwent HCT between 2018 and 2020. We have included all costs from admission day until D + 180. We used a lognormal regression. Median age was 53 y/o and most donors were unrelated (51%). Costs were higher with haploidentical donor (42%, p = 0.017, compared with URD), higher HCT-CI (15% for each point, p = 0.0056), and in patients with liver or gastrointestinal GVHD (45%, p = 0.033), and lower in patients who received CD34 > 2.5 × 10E6/kg (42%, p = 0.0038). We built a score based on the following risk factors: HCT-CI > 3, CD34 ≤ 2.5 × 10E6/kg, haploidentical donor, and donor age > 30 y/o. Patients with 2 + risk factors (N = 53) had a median cost of USD 226,156.00, compared with USD 93,048.00 in patients with zero or 1 point (N = 26, p < 0.0001). In summary, we have shown that HCT costs are higher with lower doses of CD34 cells, haploidentical HCT (provided that the costs of stem cell procurement and ATG are not included), and in patients with higher HCT-CI. Prospective and refined cost analyses comparing haploidentical and URD transplants, as well as effective strategies for patients with higher HCT-CI scores, are warranted. We found no difference in costs between URD and MSD transplantation.

Impact of Treatment Prior to Allogeneic Transplantation of Hematopoietic Stem Cells in Patients with Myelodysplastic Syndrome: Results of the Latin American Bone Marrow Transplant Registry.

It has been suggested that bridging therapy with intensive chemotherapy and/or hypomethylating agents followed by hematopoietic stem cell transplantation (HSCT) can be valuable in the treatment of patients with myelodysplastic syndromes (MDS). However, the influence of this approach on HSCT outcomes remains poorly defined. Therefore, our objective was to investigate the influence of treatment before HSCT in patients with MDS. We retrospectively analyzed data from the Latin American registry of 258 patients from 17 Latin American centers who underwent HSCT from 1988 to 2019. Our data showed that there was pre-HSCT. We detected no significant difference regarding the impact on overall survival of treated and untreated patients before HSCT. Despite these data, the type of previous treatment among treated patients showed a significant difference in overall survival. Treatment with hypomethylating agents together with pre-HSCT chemotherapy seems to result in better survival of the studied population. These data correspond to the first results obtained through cooperative work between various centers in Latin America comparing the different approaches to patients and reflecting their reality and challenges. Therefore, the selection of pretransplant bridge therapy should be analyzed and focus given primarily to those approaches that result in better survival of patients with MDS.

Hematopoietic cell transplantation in pediatric patients with acute leukemias or myelodysplastic syndrome using unrelated adult or umbilical cord blood donors in Brazil.

The choice of alternative donors for HCT for patients without an HLA-matched related donor depends on several factors. We compared major HCT outcomes in 212 consecutive children transplanted at 11 centers in Brazil for acute leukemia or MDS from an HLA-matched unrelated donor (MUD, n = 95), mismatched unrelated donor (MMUD, n = 47) or unrelated umbilical cord blood (UCB, n = 70). Most had ALL (61%), bone marrow (57%) as the graft source and 95% received a MAC regimen. The 3-year OS probability were 57, 55, and 37% after HCT from MUD, MMUD, and UCB, respectively (HR 1.68, 95%CI 1.07-2.63; P = .02). In comparison with MUD, OS was similar after transplantation of a ≥ 6/8 HLA-matched or a high cell dose (>5 × 107 TNC/kg) CB unit (HR 1.41, 95%CI 0.88-2.27; P = .15). NRM was higher for UCB (HR 3.90, 95%CI 1.43-10.7; P = .01) but not for MMUD (HR 1.03, 95%CI 0.53-2.00; P > .20). Advanced disease (HR 2.05, 95%CI 1.26-3.33; P < .001) and UCB with high probability of being < 6/8 HLA-matched (HR 5.34, 95%CI 2.0-13.9; P < .001) were associated with higher mortality. Relapse and acute GVHD were similar among groups, while PGF was higher among UCB transplants (P = .002) and chronic GVHD among MMUD group (HR 2.88, 95% CI 1.05-7.88; P = .04). Our results suggest that in Brazil HCT outcomes performed with MMUD and MUD donors were comparable, while with UCB units < 6/8 HLA-matched were associated with higher NRM for children with acute leukemia or MDS.

Retrospective study of the digestive tract mucositis derived from myeloablative and non-myeloablative/reduced-intensity conditionings with busulfan in hematopoietic cell transplantation patient.

Busulfan is a major component of chemotherapy conditioning in hematopoietic cell transplantation (HCT). This alkylating agent is highly toxic at myeloablative doses, exposing HCT patients to risks of mortality. Non-myeloablative (NMA) and reduced-intensity conditioning (RIC) using busulfan have shown impaired toxicity. However, the toxicity of NMA/RIC in the digestive tract is poorly described. This study aimed to characterize the mucositis in the oral cavity (OM), oropharynx/esophagus, and gastrointestinal tract derived from conditionings with myeloablative and non-myeloablative doses of busulfan. We retrospectively retrieved clinical data of HCT patients (n = 100) who underwent myeloablative conditioning (MAC) or NMA/RIC with busulfan. Frequency and time duration of mucositis in the oral cavity and oropharynx/esophagus, diarrhea, and prescription of total parenteral nutrition (TPN) and opioids were also collected. OM severity (p = 0.009) and time duration of mucositis in oropharynx/esophagus (p = 0.022) were frequently higher in MAC than NMA/RIC. A myeloablative dose of busulfan was a risk factor for OM grade ≥ 2 (OR = 4.8, p = 0.002) and for mucositis in oropharynx/esophagus ≥ 5 days (OR = 2.64, p = 0.035). A longer duration of mucositis in the oropharynx/esophagus was also associated with an increase in the prescription of opioids (OR = 7.10, p < 0.001).Overall survival (OS) in MAC was significantly higher than that in NMA/RIC (p = 0.017). No variables related to mucositis interfere significantly in OS. In conclusion, myelosuppression in busulfan-based regimens are predisposed to a high risk for severe OM and to prolonged mucositis in the oropharynx/esophagus.