Characterization of buffy-coat-derived granulocytes for clinical use: - identifying clinical and laboratory parameters for decision making

Rationale:
Life-threatening infections continue to be a consequence of prolonged severe
neutropenia (<0.5x109/L neutrophils), which most commonly occur in case of
intensive chemotherapy for hematological malignancies, during conditioning for
myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) and
during intensified immunosuppression due to graft-versus-host disease. The
associated invasive infections with bacteria and fungi (i.e. yeasts and molds),
with the latter being increasingly resistant to antifungal therapy, lead to
high morbidity, intensive care treatment and - often - ensuing death. Moreover,
intensified and prolonged antifungal therapy in patients after allogeneic HSCT
often interferes with immunosuppressive therapy resulting in liver- and renal
toxicity. In this respect administration of donor neutrophilic granulocytes
(polymorphonuclear neutrophils, PMNs) is a logical but still unproven
experimental therapy. Prophylactic use of granulocyte transfusions (GTX) has
been accepted to be of limited value in clinical practice. In contrast, the use
of therapeutic GTX to resolve existing infections has been shown to be
effective. However, this approach has not gained lasting acceptance over the
years. This may be explained by technical issues (yield, neutrophil activation
during isolation, etc), or it may be related to the fact that GTX is often
considered too late, i.e. with the patient in a deplorable state or due to the
fear to induce anti-HLA antibodies in patients facing a allogeneic HSCT.
Surrogate markers in patient plasma may help to identify patients which will
benefit from GTX and may help to exclude patients at high risk for transfusion
associated complications.

• To find surrogate markers in plasma in order to identify patients, which may
benefit from granulocyte transfusions and which are at risk for transfusion
complications.
• To determine - in combination with the outcomes of the NEPTUNIS study -
markers released during neutropenia and neutropenic fever in plasma of patients
undergoing high-dose chemotherapy due to hematological malignancies.
• To develop a predictive model of biomarkers to distinguish between a sterile
inflammation and an infection during febrile neutropenia.

Study design: prospective follow up study

There is no burden. The twice weekly or every 48 hour sample collections will
be planned as much as possible together with regular blood drawings. If somehow
that*s not possible, an extra venipuncture is necessary.