Search

We evaluated early and late hematopoietic reconstitution in 27 patients with advanced lymphoma, Hodgkin’s disease, and breast or ovarian cancer after treatment using high-dose/myeloablative conditioning regimens and autologous peripheral blood stem cell (PBSC) transplantation. Eighteen patients (67%) received G-CSF 5 μ g/kg/day following chemotherapy and nine (33%) were mobilized using G-CSF alone. Each patient had 7 × 108 mononuclear cells (MNC) per kg collected. G-CSF was administered post-PBSC infusion. While all patients showed prompt granulocyte recovery by day 14, platelet recovery failed to occur in four (15%) heavily pretreated patients with non-Hodgkin’s lymphoma. Retrospective analysis in 17 patients revealed that the infused number of CD34 surface antigen-positive cells correlated with time to granulocyte (r = 0.59, P = 0.012) and platelet (r = 0.58, P = 0.021) recovery. Patients receiving the higher numbers of CD34+ cells had consistently better hematologic parameters at all times examined. At 180 days post-transplant, the median Hb level was 124 g/l vs 88 g/l (P = 0.004); platelet count was 202 × 109/l vs 25 × 109/l (P = 0.004); and neutrophil count was 3100 × 106/l vs 1400 × 106/l (P = 0.15). Hemoglobin strongly correlated with the CD34+ cell dose at 360 days (r = 0.90, P = 0.01). We conclude that graft CD34+ cell content appears to be an indicator of the quality of late as well as early hematopoietic function. [ABSTRACT FROM AUTHOR]

The combination of busulfan and cyclophosphamide has seldom been employed as a conditioning regimen for patients with lymphoma. Twenty patients with relapsed or refractory lymphoma were treated with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (BU/CY) followed by peripheral blood stem cell rescue in 19 patients or autologous bone marrow in one patient. There were 12 females and eight males, with a median age of 48 years (range 30–65). Four patients had Hodgkin’s disease, and 16 patients had non-Hodgkin’s lymphoma. Disease status at the time of BU/CY was: first relapse in 10 patients (four patients with chemosensitive disease and six patients with chemoresistant disease), primary refractory disease in six patients, and more advanced disease in four patients. Excessive treatment-related toxicity was not noted. There were no cases of interstitial pneumonitis, but three cases of veno-occlusive disease occurred. At 2 years, the estimated overall survival and event-free survival are 50% and 33%. We concluded that BU/CY seems to have sufficient anti- lymphoma activity, is devoid of excessive toxicity and warrants further investigation in this patient population. [ABSTRACT FROM AUTHOR]

A 32-year-old male received an allogeneic peripheral blood stem cell transplant (alloPBSCT) for myelodysplasia from his one HLA-A antigen mismatched brother. He is alive with trilineage engraftment and without active GVHD 200 days after transplant. In July 1986 he underwent orthotopic cardiac transplantation for viral cardiomyopathy and has received continuous immunosuppressive therapy. A post-transplant lymphoproliferative disorder with Hodgkin-like histopathology was diagnosed in August 1993 and was successfully treated with four cycles of MOPP chemotherapy. Due to persistent pancytopenia he underwent a bone marrow aspiration and biopsy in May 1996 which revealed monosomy 7 and morphologic changes compatible with myelodysplasia. This is the first report of a cardiac transplant recipient receiving an allogeneic hematopoietic stem cell transplant. [ABSTRACT FROM AUTHOR]

Chimerism test was evaluated to predict leukemia relapse. Increasing mixed chimerism (IMC), defined as recipient increase ≥0.1% in peripheral blood total cell chimerism, was used as a surrogate of disease activity. Combination of quantitative PCR and short-tandem repeat method was applied to achieve high assay sensitivity. Total of 184 patients received stem cell transplant for acute myeloid leukemia (N = 110), acute lymphocytic leukemia (N = 41), myelodysplastic syndrome (N = 30), and 2389 chimerism tests (median follow-up, 1054 days). Sixty-six patients relapsed, and 118 patients did not. Cumulative incidence of relapse increased after 1 IMC or ≥2 consecutive IMCs (hazard ratios, 9.9 and 44.4, respectively). Predicted percentage relapse by day 30 after IMC was 0% (0 IMC), 10% (1 IMC), and 40% (≥2 IMCs). The last chimerism results before relapse detected IMC in 57 of 66 relapsed patients (sensitivity, 86.4%). Nine patients had no IMC before relapse (false negative) because of rapidly evolving relapse (N = 4) or extramural relapse (N = 5). In 118 patients without relapse, 158 of 1873 tests detected IMC (false positive, 8.4%; specificity, 91.6%). The false-positive rates increased with higher percentage recipient T-cell chimerism levels, indicating T-cell contamination as a cause. Chimerism monitoring predicts relapse. However, caution must be taken for false-positive or false-negative IMCs. T-cell removal can improve chimerism test specificity in patients with mixed T-cell chimerism., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Primary graft failure (PGF) and multi-lineage cytopenia (MLC) increase the risk of nonrelapse mortality in allogeneic hematopoietic cell transplants (HCT). We evaluated the impact of post-transplant cyclophosphamide (PTCy) and splenomegaly on PGF and MLC for hematological malignancies. This study included patients with PTCy (N=84) and conventional graft-vs.-host disease prophylaxis (N=199). The occurrence of splenomegaly varied widely, ranging from 17.1 % (acute myeloid leukemia) to 66.7 % (myeloproliferative neoplasms). Ten patients (N=8 in the PTCy and N=2 in the non- PTCy) developed PGF, and 44 patients developed MLC (both N=22). PTCy and severe splenomegaly (≥20 cm) were risk factors for PGF (odds ratio (OR): 10.40, p<0.01 and 6.74, p=0.01 respectively). Moreover, severe splenomegaly was a risk factor for PGF in PTCy patients (OR: 10.20, p=0.01). PTCy (hazard ratio (HR) 2.09, p=0.02), moderate (≥15, <20 cm, HR 4.36, p<0.01), and severe splenomegaly (HR 3.04, p=0.01) were independent risk factors for MLC. However, in subgroup analysis in PTCy patients, only mild splenomegaly (≥12, <15 cm, HR 4.62, p=0.01) was a risk factor for MLC. We recommend all patients be screened for splenomegaly before HCT, and PTCy is cautioned in those with splenomegaly., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest associated with this manuscript., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Bacterial prophylaxis with a fluoroquinolone (FQ) during autologous stem cell transplant (ASCT) is common, although not standardized among transplant centers. The addition of doxycycline (doxy) to FQ prophylaxis was previously linked to reduced neutropenic fever and bacteremia in multiple myeloma (MM) patients undergoing ASCT although several confounders were present. We compared the incidence of neutropenic fever and bacteremia between MM patients variably receiving prophylaxis with FQ alone and FQ-doxy during ASCT., Methods: Systematic retrospective chart review of MM patients who underwent ASCT between January 2016 and December 2021. The primary objective was to determine the effect of bacterial prophylaxis on neutropenic fever and bacteremia within 30 days of ASCT. Multivariable logistic regression for neutropenic fever and univariate logistic regression for bacteremia accounted for differences in subject characteristics between groups., Results: Among 341 subjects, 121 received FQ and 220 received FQ-doxy for prophylaxis. Neutropenic fever developed in 67 (55.4%) and 87 (39.5%) subjects in the FQ and FQ-doxy groups, respectively (p = .005). Bacteremia was infrequent, with 5 (4.1%) and 5 (2.3%) cases developing in the FQ and FQ-doxy groups, respectively (p = .337). Among Gram-negative bacteremia events, 7/7 Escherichia coli strains were FQ-resistant, and 5/7 were ceftriaxone-resistant., Conclusion: The FQ-doxy prophylaxis group had fewer cases of neutropenic fever than the FQ group, however, there was no significant difference in bacteremia. High rates of antibiotic resistance were observed. An updated randomized controlled trial investigating appropriate prophylaxis for ASCT in the context of current oncology standards and changing antimicrobial resistance rates is warranted., (© 2024 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)