New strategies of allogeneic hematopoietic stem cell transplantation with the use of haploidentical donors

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for patients with hematological diseases. The probability of finding a human leucocyte antigen (HLA) identical donor among family members is around 25% and 30% that of having a full matched unrelated donor in the registry. For patients lacking a full matched sibling or unrelated donor, several strategies are available to benefit of mismatched donors, such as haploidentical family donors. Recently, novel strategies to control graft-versus-host disease and facilitate engraftment extended the use of unmanipulated haploidentical stem cell transplantation, both in the myeloablative and reduced intensity conditioning regimen and using bone marrow or peripheral blood stem cell as stem cell source. This review presents the different transplant platform available in the setting of haploidentical transplantation for patients with hematological malignancies. It provides also criteria for the choice of the haploidentical donors. Prospective comparative studies are required to establish the relative efficacy of different transplant platforms. Moreover, center experience and facilities and the availability of clinical trials should be taken in consideration for the appropriate algorithm of donor choice

Features of Toxoplasma gondii reactivation after allogeneic hematopoietic stem-cell transplantation in a high seroprevalence setting

We performed a single-centre retrospective study to evaluate the effectiveness of Toxoplasma gondii prevention strategies after allogeneic stem-cell transplantation. The charts of 138 allogeneic stem-cell recipients over a 4-year period were reviewed. Forty-nine percent of patients were not receiving optimal trimethoprim–sulfamethoxazole (TMP–SMZ) prophylaxis at day +30, mainly due to persistent cytopenia. Six months after transplantation, the rate of toxoplasmosis reactivation was 11.6%, including nine cases of Toxoplasma infection and seven cases of Toxoplasma disease. Fifty-six percent of cases of reactivation occurred before day +30. Thirty-eight percent occurred in patients receiving atovaquone prophylaxis. In 57% of patients presenting with Toxoplasma disease, signs of disease were present at first evidence of Toxoplasma DNA in peripheral blood samples. This study illustrates the limitations inherent to currently used toxoplasmosis prevention strategies and argues for the use of a combined prophylactic and preemptive approach. After performing the initial study, we limited the use of atovaquone in favour of TMP–SMZ when possible, and implemented an early prevention strategy consisting of the introduction of prophylaxis starting on day of engraftment. Over the following 16 months, 88.9% of eligible Toxoplasma-seropositive patients were receiving TMP–SMZ at day +30, and the rate of early Toxoplasma reactivation was 1.5%

Impact of gut fungal and bacterial communities on the outcome of allogeneic hematopoietic cell transplantation

Patients receiving allogeneic hematopoietic cell transplantation (alloHCT) were previously shown to display a bacterial gut dysbiosis; however, limited data are available regarding the role of fungal microbiota in these patients. We evaluated the bacterial and fungal composition of the fecal microbiota at day 0 of alloHCT. Higher bacterial diversity was associated with an improved overall survival (OS) and disease-free survival (DFS). While fungal diversity had no impact on patient outcomes, we observed that high versus low relative abundance of Candida albicans in alloHCT patients at day 0 was associated with a significantly lower OS, DFS and graft-versus-host-free, relapse-free survival (GRFS) (p = 0.0008, p = 0.0064 and p = 0.026, respectively). While these results are limited by low patient numbers and low fungal read counts in some samples, they suggest a potentially important role for C albicans in alloHCT