Thrombopoietin Receptor Agonists for Severe Thrombocytopenia after Allogeneic Stem Cell Transplantation: Experience of the Spanish Group of Hematopoietic Stem Cell Transplant.

Persistent thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Romiplostim and eltrombopag are the currently available thrombopoietin receptor agonists (TPO-RAs), and some studies with very small numbers of cases have reported their potential efficacy in the allo-SCT setting. The present retrospective study evaluated the safety and efficacy of TPO-RAs in 86 patients with persistent thrombocytopenia after allo-HSCT. Sixteen patients (19%) had isolated thrombocytopenia (PT), and 71 (82%) had secondary failure of platelet recovery (SFPR). TPO-RA therapy was started at a median of 127 days (range, 27 to 1177 days) after allo-SCT. The median initial and maximum administered doses were 50 mg/day (range, 25 to 150 mg/day) and 75 mg/day (range, 25 to 150 mg/day), respectively, for eltrombopag and 1 µg/kg (range, 1 to 7 µg/kg) and 5 µg/kg (range, 1 to 10 µg/kg), respectively, for romiplostin. The median platelet count before initiation of TPO-RA therapy was 14,000/µL (range, 1000 to 57,000/µL). Platelet recovery to ≥50,000/µL without transfusion support was achieved in 72% of patients at a median time of 66 days (range, 2 to 247 days). Eighty-one percent of the patients had a decreased number of megakaryocytes before treatment, showing a slower response to therapy (P = .011). The median duration of treatment was 62 days (range, 7 to 700 days). Grade 3-4 adverse events (hepatic and asthenia) were observed in only 2% of the patients. At last follow-up, 81% of patients had discontinued TPO-RAs and maintained response, and 71% were alive. To our knowledge, this is the largest series analyzing the use of TPO-RAs after allo-SCT reported to date. Our results support the efficacy and safety in this new setting. Further prospective trials are needed to increase the level of evidence and to identify predictors of response.

Usefulness of thrombopoietin receptor agonists for persistent clinically relevant thrombocytopenia after allogeneic stem cell transplantation.

OBJECTIVE AND METHODS: Severe postengraftment thrombocytopenia is a common complication after allogeneic stem cell transplantation (alloSCT). A few studies have suggested that the use of thrombopoietin agonists (TPOa) may be useful in this setting. Our retrospective study is the largest series published to date; we retrospectively evaluated TPOa efficacy and safety in 20 adult alloSCT recipients who received TPOa as a compassionate use for clinically relevant thrombocytopenia. RESULTS: Twelve of 20 patients (60%) responded, with a 180-day cumulative incidence of successful platelet recovery to ≥30 and ≥50 × 109 /L of 57% (95% CI: 44%-71%) and 32% (95% CI: 18%-46%), respectively, which were reached at a median of 28 and 34 days from the start of therapy. Fifty percent of the responders were able to discontinue the TPOa without recurrence of severe thrombocytopenia and its associated hemorrhagic complications. No serious adverse events were reported. Possible variables associated with higher response to TPOa were as follows: age < 40 years, presence of megakaryocytes in the bone marrow aspirate, and/or prior response to other hematopoietic growth factors. CONCLUSION: This study adds further enthusiasm for continued research on the use of these agents for the treatment of persistent thrombocytopenia in alloSCT recipients.

Synchronizing the use of allogeneic hematopoietic cell transplantation in checkpoint blockade therapy for Hodgkin lymphoma.

INTRODUCTION: The use of checkpoint blockade therapy (CBT) has shown impressive results for the treatment of relapsed/refractory Hodgkin lymphoma (cHL). The impact of CBT depends on the reversal of an exhausted T-cell immune phenotype and a consequential increase in the immunological, anti-tumor effect derived from a patient's adaptive immunity. As most patients with classical Hodgkin lymphoma will relapse during or after this treatment, clinicians often provide consolidation with allogeneic hematopoietic cell transplantation (alloHCT) in fit patients. However, the mechanisms responsible for CBT efficacy can also be those that increase the risk of immunological complications after alloHCT. AREAS COVERED: We carried out in-depth research on the current medical literature to report and discuss the mechanism of action of CBT within a cHL setting; clinical results of CBT in cHL setting pre-alloHCT and post-alloHCT; interactions between CBT and alloHCT; and further clinical considerations. EXPERT OPINION: Checkpoint blockade therapy is an effective strategy for relapsed/refractory cHL. Its use is associated with higher immunological toxicities when administered before or after alloHCT. Whenever alloHCT is planned, clinicians should follow international recommendations such as using post-transplant cyclophosphamide GVHD prophylaxis.

Feasibility of thiotepa addition to the fludarabine-busulfan conditioning with tacrolimus/sirolimus as graft vs host disease prophylaxis.

In classical reduced-intensity conditioning (RIC) regimens, including the fludarabine and busulphan (BF) combination, sirolimus and tacrolimus (SIR-TAC) as graft vs host disease (GVHD) prophylaxis has shown acceptable results. The outcomes of SIR-TAC in a more intense RIC regimen as Thiotepa-fludarabine-busulfan (TBF) have been hardly investigated. This retrospective study included all consecutive patients receiving an allogeneic hematopoietic stem cell transplantation for myeloid malignancies (January 2009-2017) conditioned with either TBF or BF and receiving SIR-TAC. Patients receiving TBF presented higher non-relapse mortality (31.6 vs 12.3%, p = .01), along with shorter overall survival (51.8% vs 77.8%, p < .01) at 2 years than patients treated with BF. There were no significant differences in the cumulative incidence of grade II-IV acute GVHD or moderate-severe chronic GVHD or relapse between both groups. These results suggest that TBF does not seem to improve the traditional RIC BF regimen, at least when associated with SIR-TAC prophylaxis.

Ultrastructural, cytogenetic, and molecular findings in mast cell leukemia: Case report.

We report a de novo aleukemic form of MCL with a complex monosomic karyotype with LOH for multiple chromosomes and TP53 mutation. Additionally, whereas D816V KIT was not found, the c-Kit transmembrane domain p.M541L variant was detected which is the most common SNP of KIT gene in humans with controversial pathogenic role. In these cases, it is crucial to perform a rapid broad molecular study for an accurate diagnosis which could help to initiate targeted therapy.