NCCN Guidelines® Insights: Hematopoietic Growth Factors, Version 1.2022.

The NCCN Guidelines for Hematopoietic Growth Factors provide recommendations for the appropriate use of growth factors in the clinical management of febrile neutropenia (FN), chemotherapy-induced thrombocytopenia (CIT), and chemotherapy-induced anemia (CIA). Management and prevention of these sequelae are an integral part of supportive care for many patients undergoing cancer treatment. The purpose of these guidelines is to operationalize the evaluation, prevention, and treatment of FN, CIT, and CIA in adult patients with nonmyeloid malignancies and to enable the patient and clinician to assess management options for FN, CIT, and CIA in the context of an individual patient's condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for Hematopoietic Growth Factors, with particular emphasis on the incorporation of a newly developed section on CIT.

Considerations for Use of Hematopoietic Growth Factors in Patients With Cancer Related to the COVID-19 Pandemic.

Hematopoietic growth factors, including erythrocyte stimulating agents (ESAs), granulocyte colony-stimulating factors, and thrombopoietin mimetics, can mitigate anemia, neutropenia, and thrombocytopenia resulting from chemotherapy for the treatment of cancer. In the context of pandemic SARS-CoV-2 infection, patients with cancer have been identified as a group at high risk of morbidity and mortality from this infection. Our subcommittee of the NCCN Hematopoietic Growth Factors Panel convened a voluntary group to review the potential value of expanded use of such growth factors in the current high-risk environment. Although recommendations are available on the NCCN website in the COVID-19 Resources Section (https://www.nccn.org/covid-19/), these suggestions are provided without substantial context or reference. Herein we review the rationale and data underlying the suggested alterations to the use of hematopoietic growth factors for patients with cancer in the COVID-19 era.

NCCN Guidelines Insights: Hematopoietic Growth Factors, Version 1.2020.

Management of febrile neutropenia (FN) is an integral part of supportive care for patients undergoing cancer treatment. The NCCN Guidelines for Hematopoietic Growth Factors provide suggestions for appropriate evaluation, risk determination, prophylaxis, and management of FN. These NCCN Guidelines are intended to guide clinicians in the appropriate use of growth factors for select patients undergoing treatment of nonmyeloid malignancies. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines regarding the incorporation of newly FDA-approved granulocyte-colony stimulating factor biosimilars for the prevention and treatment of FN.

The impact of pre-transplant valganciclovir on early cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation.

Cytomegalovirus reactivation is a common complication of allogeneic hematopoietic stem cell transplant. The use of pre-transplant valganciclovir during the conditioning regimen followed by preemptive therapy has been used in an attempt to reduce the rate of early cytomegalovirus reactivation, but efficacy data are lacking. In this retrospective study, we evaluated the impact of pre-transplant valganciclovir during the conditioning regimen followed by a preemptive approach on the rate of early cytomegalovirus reactivation through day 100. The rate of cytomegalovirus reactivation through day 100 was 41% in the no-valganciclovir group compared to 46% in the valganciclovir group (p = 0.4). Interestingly, median time to cytomegalovirus reactivation was earlier in the no-valganciclovir group compared to the valganciclovir group (26 vs. 34 days; p = 0.008) and there was a trend toward a higher rate of cytomegalovirus disease through day 100 in the no-valganciclovir group (0.7% valganciclovir vs. 4% no-valganciclovir; p = 0.1). Day 100 survival was similar between the groups (90% valganciclovir vs. 91% no-valganciclovir; p = 0.8). Although the time to cytomegalovirus reactivation is significantly longer in the valganciclovir group, this did not impact the rate of cytomegalovirus reactivation or survival by day 100 suggesting that other strategies need to be explored.

A randomized phase III study of pretransplant conditioning for AML/MDS with fludarabine and once daily IV busulfan ± clofarabine in allogeneic stem cell transplantation.

Pretransplant conditioning with Fludarabine (Flu)-Busulfan (Bu) is safe, but clofarabine (Clo) has improved antileukemic activity. Hypothesis: Flu+Clo-Bu (FCB) yields superior progression-free survival (PFS) after allogeneic transplantation. We randomized 250 AML/MDS patients aged 3-70, Karnofsky Score ≥80, with matched donors, to FCB (n = 120) or Flu-Bu (n = 130), stratifying complete remission (CR) vs. No CR, (NCR). HCT-CI scores varied, from 0 to 10. All evaluable patients engrafted. Median follow-up was 66 months (interquartile range: 58-80). Three-year relapse incidence (RI), 25% with FCB, vs. 39% with Flu-Bu (p = 0.018), offset by higher non-relapse mortality, 22.6% (95%CI: 16-30.2%) vs. 12.3% (95%CI: 6.5-19%). Three-year PFS was 52% (95%CI: 44-62%) (FCB), vs. 48% (95%CI: 41-58%) (Flu-Bu). FCB benefited CR patients less, NCR patients age ≤ 60 had 3-year 34% RI (95%CI: 19-49%) (FCB) vs. 56% (95%CI: 38-70%) after Flu-Bu (p = 0.037). NCR patients >60 years had 3-year RI 10.0% (FCB), vs. 56.0%, after Flu-Bu (p = 0.003). Bayesian regression analysis including treatment-covariate interactions showed FCB superiority in NCR patients with low HCT-CI (0-2). Serious adverse event profiles were similar for the regimens. Conditioning with FCB did not improve PFS overall, but improved disease control in NCR patients, mandating confirmatory trials. Remission status and HCT-CI should be considered when using FCB.

Leukemia cell mobilization with G-CSF plus plerixafor during busulfan-fludarabine conditioning for allogeneic stem cell transplantation.

We hypothesized that during conditioning chemotherapy for allogeneic stem cell transplant (allo-SCT), the disruption of stromal-leukemia interactions using G-CSF in combination with the CXCR4-specific inhibitor, plerixafor, may promote the release of leukemic cells from the niche and increase tumor elimination. In a phase 1/2 investigation, we treated 45 AML/myelodysplastic syndrome (MDS)/CML patients (34 AML, 7 MDS and 4 CML) with G-CSF (10 µg/kg daily for 6 days starting on day -9) plus plerixafor (doses of 0, 80, 160 or 240 µg/kg daily for 4 days starting on day -7) along with the busulfan-fludarabine (Bu-Flu) conditioning regimen. In the phase 1 part, we determined that G-CSF plus plerixafor is safe in this setting. We compared the clinical effects and outcomes of AML/MDS study patients (n=40) with 164 patients from a historical data set who received Bu-Flu alone before allo-SCT by stratifying on cytogenetics and disease status to correct for bias. Study patients had increased myeloid chimerism and lower rates of GvHD. There was no significant difference in relapse-free survival or overall survival. The G-CSF plus plerixafor combination increased circulating WBCs, CD34+ cells and CXCR4+ cells, and preferentially mobilized FISH+ leukemic cells.

West Nile encephalitis in 2 hematopoietic stem cell transplant recipients: case series and literature review.

Most human cases of West Nile virus infection are acquired via bites from an infected mosquito. In some cases, infection may also be transmitted by infected blood products or transplanted organs. There have been recent publications suggesting that chemotherapy and immunosuppression may increase a person's risks of developing central nervous system disease if the person is infected with the West Nile virus. Because patients undergoing hematopoietic stem cell transplantation not only are immunocompromised, but also receive multiple blood products, they are at a particularly high risk for acquiring symptomatic disease if exposed to the West Nile Virus. We describe here 2 patients who underwent hematopoietic transplantation at our institution and subsequently developed fatal West Nile virus infections.

Thalidomide for the treatment of relapsed and refractory multiple myeloma.

Thalidomide is the first drug in over 20 years to demonstrate clinically significant activity in patients with multiple myeloma. Although the survival rate has not improved with conventional chemotherapy over the last 30 years, thalidomide has produced favorable responses in patients for whom most available therapies have failed, such as those whose disease was resistant or relapsed after standard and high-dose treatments. Despite the risk of adverse effects such as sedation and constipation, thalidomide has become an alternative therapy for patients with relapsed or refractory disease. New trials with thalidomide administered alone and in combination with other agents seem to show promise in patients with multiple myeloma, as do preliminary studies with thalidomide derivatives.

Recurrent peripheral arterial thrombosis induced by cisplatin and etoposide.

A 64-year-old woman receiving intravenous chemotherapy for stage IIIB non-small cell lung cancer experienced acute arterial thrombosis of the distal radial and entire ulnar arteries with subsequent arterial occlusion of the right popliteal artery. Two separate arterial occlusions occurred after administration of cisplatin and etoposide chemotherapy; the second occlusion occurred after rechallenge with the second cycle of chemotherapy. Although venous thrombosis is more common in patients with cancer than in the general population, chemotherapy-induced arterial thrombosis rarely has been reported. To our knowledge, peripheral arterial occlusion after the first and second cycles of platinum-based chemotherapy has not been reported in the literature.