Background: For most patients with acute myeloid leukemia (AML) harboring a trisomy 8 an allogeneic hematopoietic stem cell transplantation (HSCT) is a suitable and recommended consolidation therapy. ...However, comparative outcome analyses between patients with and without trisomy 8 undergoing allogeneic HSCT have not been performed so far. Methods: We retrospectively analyzed clinical features, outcomes, and measurable residual disease (MRD) of 659 AML (12%, n = 81, with a trisomy 8) patients subjected to allogeneic HSCT as a consolidation therapy. Results: The presence of a trisomy 8 associated with a trend for higher age at diagnosis, AML of secondary origin, lower white blood cell counts at diagnosis, worse ELN2017 genetic risk, wild-type NPM1, and mutated IDH1/2 and JAK2. Outcomes after allogeneic HSCT in the entire cohort did not differ between patients with a sole trisomy 8, trisomy 8 with additional cytogenetic aberrations or without a trisomy 8. A trisomy 8 did not affect outcomes within the three ELN2017 risk groups. In accordance with findings in unselected patient cohorts, persistent MRD at allogeneic HSCT in patients with a trisomy 8 identified individuals with a higher risk of relapse following allogeneic HSCT. Conclusions: Outcomes of trisomy 8 patients after allogeneic HSCT did not compare unfavorably to that of other AML patients following allogeneic HSCT. Rather than the presence or absence of a trisomy 8, additional genetic aberrations and MRD at HSCT define outcome differences and aid in informed treatment decisions.
Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) and
treatment-related acutemyeloid leukemia (tAML) after chemotherapy or radiation therapy
for other neoplasms are associated with ...poor outcomes. CPX-351, a dual-drug liposomal
encapsulation of daunorubicin and cytarabine, has been shown to improve outcomes
in AML-MRC and tAML compared with standard 7+3 regimens. Here we report the
cases of four consecutive patients with AML-MRC or tAML who received CPX-351
as outpatient induction therapy immediately followed by allogeneic hematopoietic stem
cell transplantation (allo-HSCT). Two patients received allo-HSCT in remission (one in
complete remission and one in partial remission) and two patients received allo-HSCT
in aplasia (one at 11 days and one at 52 days after the start of induction therapy with
CPX-351). With a median follow-up of 188 days after allo-HSCT, all but one patient are
alive and two are in remission. Further studies will help define and expand the role of
CPX-351 in the treatment of AML-MRC and tAML, especially in patients expected to
undergo allo-HSCT.
Sezary Syndrome (SS) is a rare leukemic variant of primary cutaneous T-cell lymphoma.
Relapsed or refractory disease is generally considered incurable by conventional
therapeutic approaches, although ...durable responses can be achieved with novel
monoclonal antibodies. Allogeneic hematopoietic stem cell transplantation (alloHSCT)
may have potential value by inducing graft vs-lymphoma (GvL) effects, but there is
currently no consensus regarding the timing of alloHSCT or type of conditioning
regimen. Here we present the case of a male patient who achieved a complete
remission (CR) of primary refractory SS after non-myeloablative alloHSCT. Patient: Two
years prior to HSCT, the patient had been refractory to CHOEP-based chemotherapy,
interferon, extracorporeal photopheresis (ECP), and bexarotene. Directly prior to
alloHSCT brentuximab-vedotin (BV) was applied resulting in a partial remission of the
skin compartment and overall in a stable disease. Prior to HSCT, flow cytometry of the
bone marrow and peripheral blood showed an infiltration with T-cells positive for CD5,
CD4, low CD3, low CD2 and negative for CD7, CD38, HLA-DR and CD8. The trephine
biopsy showed a 7% infiltration of SS cells. The CD4:CD8 ratio in peripheral blood (pb)
was massively increased at 76.67, with 63.5% of white blood cells expressing a SS
immune phenotype. The conditioning regimen included 30 mg/m2 fludarabine on days -5,
-4 and -3 and total body irradiation with 2 Gy on day -1. Immunosuppression consisted of
cyclosporine A from day-1 and mycophenolate mofetil from day 0. The patient received
6.55x106 CD34+ cells and 1.11x108 CD3+ cells/kg body weight. Bone marrow
evaluation on day 28 still showed persistent SS cells by flow cytometry. After tapering
immunosuppression until day 169, the CD4:CD8 ratio in pb normalized. CR was
documented on day 169 after alloHSCT and is now ongoing for almost 3 years after
alloHSCT. Conclusions: We confirm that an alloHSCT can be a curative option for
refractory patients with SS. The achievement of a CR after tapering the
immunosuppressive therapy indicates a significant role of the GvL effect. In present
treatment algorithms for patients with SS, the timing of an alloHSCT and the intensity of
conditioning should be further explored.
Up to 60% of patients with aggressive B-cell lymphoma who receive chimeric antigen
receptor (CAR) T-cell therapy experience treatment failure and subsequently have a poor
prognosis. Allogeneic ...hematopoietic stem cell transplantation (alloHSCT) remains a
potentially curative approach for patients in this situation. Induction of a deep response
prior to alloHSCT is crucial for long-term outcomes, but the optimal bridging strategy
following relapse after CAR T-cell therapy has not yet been established. Polatuzumab
vedotin, an antibody drug conjugate targeting CD79b, is a novel treatment option for use in
combination with rituximab and bendamustine (Pola-BR) in relapsed or refractory disease.
Patients: We report two heavily pretreated patients with primary refractory diffuse large Bcell
lymphoma (DLBCL) and primary mediastinal B-cell lymphoma (PMBCL) respectively
who relapsed after therapy with CAR T-cells with both nodal and extranodal
manifestations of the disease. After application of three courses of Pola-BR both
patients achieved a complete metabolic remission. Both patients underwent alloHSCT
from a human leukocyte antigen (HLA)-mismatched donor following conditioning with
busulfan and fludarabine and are disease free 362 days and 195 days after alloHSCT
respectively. We conclude that Pola-BR can be an effective bridging therapy before
alloHSCT of patients relapsing after CAR T-cell therapy. Further studies will be necessary
to define the depth and durability of remission of this salvage regimen before alloHSCT.
Background: Ewing sarcoma is one of the most frequent soft-tissue tumors in
pediatric patients. The current treatment protocols recommend stem cell apheresis (SCA) after completion of the second ...course of induction therapy with
vincristine, ifosfamide, doxorubicine, and etoposide (VIDE). The feasibility of
SCA and graft compositions in adult patients with Ewing sarcoma have not
been previously analyzed.
Methods and Materials: The authors analyzed 29 stem cell collections of
19 adult patients (9 male, 10 female) at a median age of 27 (range 19–53) years
mobilized after VIDE (n = 17), cyclophosphamide/topotecan (n = 1) or
vincristine, dactinomycin and ifosfamide (n = 1) chemotherapy. All patients
were mobilized with filgrastim 5 μg/kg twice daily from day +7 of chemotherapy. The collections were performed if CD34+ cell count in peripheral blood
was >10/μL. The target yields were ≥4106 CD34+ cells/kg body weight.
Results: Median CD34+ cells/μL in peripheral blood before SCA were 45.8
(range 6.7–614.4)/μL. The median cumulative yields were 10.6 (range 1.5–38.8)
CD34+ cells/kg body weight and ≥2106 in all but two patients (89%). CD34,
CD3, and CD56 yields in collections after the third VIDE and after later
courses did not differ. Four patients underwent high-dose therapy with
autologous transplantation, and all were engrafted.
Discussion: Stem cell mobilization is feasible in most Ewing sarcoma patients.
Additionally, the present study's data suggest that it is safe to postpone stem
cell collection to a later VIDE chemotherapy cycle if medically indicated
Large granular lymphocyte leukemia (LGLL) represents a rare group of diseases with
considerable difficulties in their correct diagnostic workup and therapy. The major
challenges lie in their ...distinction from reactive (including autoimmune)
lymphoproliferations. Moreover, monoclonal LGL proliferative diseases are in fact a
heterogeneous group of disorders, as recognized by the three subtypes in the current
WHO classification. It distinguishes two chronic forms (the focus of this case series),
namely T-LGLL and chronic lymphoproliferative disorders of Natural Killer cells (CLPD-NK)
as well as aggressive NK-cell leukemia. In the clinical routine, the variable presentations
and phenotypes of T-LGLL and CLPD-NK are underappreciated. The relevant differential
diagnoses range from benign reactive T-cell expansions to other mature T-cell leukemias
to highly aggressive gd-lymphomas. T-LGLL or CLPD-NK patients suffer from a wide
variety of symptoms often including, but not limited to, cytopenias or classical
autoimmune phenomena. They receive treatments ranging from mere supportive
measures (e.g. antibiotics, growth factors, transfusions) over strategies of
immunosuppression up to anti-leukemic therapies. The diagnostic pitfalls range from
recognition of the subtle T-cell proliferation, repeated establishment of monoclonality,
assignment to a descript immunophenotypic pattern, and interpretations of molecular
aberrancies. Here, we report a series of selected cases to represent the spectrum of
LGLL. The purpose is to raise awareness among the scientifically or practically interested
readers of the wide variety of clinical, immunological, and phenotypic features of the
various forms of LGLL, e.g. of T-cell type, including its gd forms or those of NK-lineage. We
highlight the characteristics and courses of four unique cases from two academic centers,
including those from a prospective nationwide LGLL registry. Each case of this instructive
catalogue serves to transport a key message from the areas of (chronic inflammatory) contexts in which LGLL can arise as well as from the fields of differential diagnostics and of
various treatment options. Implications for optimization in these areas are discussed.
