How we approach a patient with symptoms of leukostasis requiring emergent leukocytapheresis

Hyperleukocytosis can induce leukostasis, which can lead to vascular obstructions (usually in the lungs and central nervous system), tumor lysis syndrome, and disseminated intravascular coagulation. Although it has not been conclusively shown to improve long‐term outcome, leukocytapheresis may be used as part of the management of hyperleukocytosis with or without leukostasis to rapidly reduce the white blood cell (WBC) burden. Since leukocytapheresis only temporarily decreases the WBC count, early initiation of more definite therapy, such as hydroxyurea and/or chemotherapy, is essential. In this article, clinical assessment of the patient's clinical status to determine the need for leukocytapheresis as well as a general guideline for management of the technical aspects and complications of the procedure are discussed.     

Leukocyte Depletion by Therapeutic Leukocytapheresis in Patients with Leukemia

Hyperleukocytosis is a complication of various leukemias and can result in life-threatening leukostasis. Critical white blood cell (WBC) counts are conventionally defined as higher than 100 × 10⁹/l in acute myeloid leukemia and > 300 × 10⁹/l in acute lymphatic leukemia and other leukemic disorders (e. g. chronic myeloid leukemia). Leukocytapheresis is a therapeutic tool to reduce leukocyte counts in patients with symptomatic or threatening leukostasis until induction chemotherapy works. In patients with temporary contraindications against cytotoxic drugs, e.g. during pregnancy, leukocytapheresis can be used as a bridging therapy until conventional chemotherapy can be started. Therapeutic leukocytapheresis should be performed in specialized centers by experienced, well-trained staff. Thorough monitoring of the patients is extremely relevant. During a single procedure, WBC count can be reduced by 10–70%. Treatment should be repeated daily and can be discontinued when the symptoms of leukostasis have been resolved and/or leukocyte counts have fallen below the critical thresholds. There are no prospective studies evaluating the clinical efficacy of therapeutic leukocytapheresis in patients with hyperleukocytosis. It can be concluded from retrospective studies that leukocytapheresis might have some beneficial effect in early morbidity and mortality of patients with newly diagnosed AML but has no influence on overall long-term survival. Induction chemotherapy is the most important treatment in these patients and must never be postponed.     

Physiological measurements corroborate symptomatic improvement after therapeutic leukapheresis in a pregnant woman with chronic myelogenous leukemia

Therapeutic leukapheresis can control the white blood cell count (WBC) of pregnant women with chronic myelogenous leukemia (CML) who have hyperleukocytosis without leukostasis. The medical justification for this treatment has not been objectively documented. We report a 27‐year‐old woman, diagnosed with CML at 10‐week gestation, who developed severe dyspnea on exertion. A workup that included chest CT and echocardiography with a bubble study detected no cardiopulmonary pathology to explain her symptoms, and thus she was referred for leukapheresis. Prior to her first leukapheresis, which lowered her WBC from 154 × 10³/μL to 133 × 10³/μL, her oxygen saturation (SpO₂) on room air decreased from 98 to 93% during 100 feet of slow ambulation and she was dyspneic. Just after the leukapheresis, her dyspnea on exertion was much improved and her SpO₂ remained at 98% with repeat ambulation. Spirometry and lung volume studies obtained before and after her first leukapheresis demonstrated 32 and 31% improvements in forced vital capacity and forced expiratory volume in 1 s respectively, a 25% increase in functional residual capacity, and a 142% improvement in expiratory reserve volume. Residual volume decreased by almost 20%. Three times in a week, leukapheresis was continued until her WBC was controlled with interferon α‐2b approximately 4 weeks later. Her dyspnea had completely resolved. She gave birth by elective caesarean section to a healthy boy at 32 weeks. Corroboration of symptom relief by leukapheresis with physiological data may justify such treatment in pregnant patients with CML. J. Clin. Apheresis 31:393–397, 2016. © 2015 Wiley Periodicals, Inc.     

Therapeutic leukapheresis in patients with leukostasis secondary to acute myelogenous leukemia

Leukostasis is a relatively uncommon but potentially catastrophic complication of acute myelogenous leukemia (AML). Prompt leukoreduction is considered imperative to reduce the high mortality rate in this condition. Leukapheresis, usually associated with chemotherapy, is an established approach to diminish blast cell counts. We report a single center experience in managing leukostasis with leukapheresis. Fifteen patients with leukostasis of 187 patients with AML (8.02%) followed at our institution were treated with leukapheresis associated with chemotherapy. The procedures were scheduled to be performed on a daily basis until clinical improvement was achieved and WBC counts were significantly reduced. Overall and early mortalities, defined as that occurred in the first 7 days from diagnosis, were reported. A high proportion of our patients with leukostasis (46.66%) had a monocytic subtype AML (M4/M5, according to French‐American‐British classification). The median overall survival was 10 days, despite a significant WBC reduction after the first apheresis procedure (from 200.7 × 10⁹/L to 150.3 × 10⁹/L). Almost half of patients (7/15) had an early death. Therapeutic leukapheresis, associated or not to chemotherapy, is an effective approach to reduce WBC counts in patients with AML and leukostasis; however, this therapeutic procedure does not appear to change significantly the sombre prognosis observed in the majority of patients with this complication. Other forms of treatment must be found to reduce the high mortality rate related to leukostasis. J. Clin. Apheresis, 2011. © 2011 Wiley‐Liss, Inc.     

Leukapheresis in 15 patients weighing 20 kg or less: A single centre experience

The application of apheresis equipment to perform leukapheresis (LK) in low weight paediatric patients is logistically complex and lacking of largest clinical performing experiences, meanwhile, the benefit from LK is controversial. In this study, 15 children with acute lymphoblastic leukemia(ALL)and acute myeloid leukemia (AML) and hyperleukocytosis were treated with the COBE Spectra apheresis system in the general paediatric ward by the staff from the department of Blood Transfusion. 26 LK procedures were performed. 12 patients (80%) were performed with peripheral veins, others (20%) with femoral veins. Median age, body weight of the patients was 4 years (range from1 year 10 month to 7 years) and 15 kg (range from10 to 20 kg). The median white blood cell (WBC) count of pre-first-LK was 289 × 10⁹/L (range from 108 × 10⁹/L to 579 × 10⁹/L). The median decrease in WBC count after each LK was 34% (range from 14% to 54%), and overall decrease in WBC after completion of LK procedures was 45% (range from 15% to 70%). All of the patients had no further signs of leukostasis and achieved marked reductions in WBC counts. Only minor clinical adverse events were attributable to LK. With adequate monitoring and experienced team, LK is a safe and may be a beneficial leukoreduction method in small patients weighing 20 kg or less with ALL and AML.     

Therapeutic cytoreduction in a 7-month-old baby with acute leukemia

A 7-month-old girl with acute biphenotypic leukemia [t(4;11)] had accompanying anemia, thrombocytopenia, and a white blood cell count of 535,000/μL with 98% blasts. Before instituting chemotherapy, therapeutic leukapheresis was done to reduce the threat of complications from leukostasis. Using a Cobe Spectra blood cell separator primed with modified blood, we processed 1,395 mL of her blood, removing 201 mL of the buffy coat containing 5.8 × 10¹⁰ white blood cells. This reduced the WBC count to 301,000/μL. Only a single procedure was done, without significant complications. The rationale of this preparatory cytoreduction is discussed critically. Subsequent chemotherapy resulted in a long-lasting remission. © 1992 Wiley-Liss, Inc.     

Safety of growth factor administration for leukapheresis in those with WBC counts greater than 60,000/µl

Purpose: Peripheral blood stem cell mobilization using growth factors is a common method of stem cell collection for transplantation, however, little is reported concerning safety of continued growth factor delivery in exceptional responders with very high white blood cell (WBC) counts in preparation for pheresis. We performed a retrospective study of the safety of growth factor delivery for leukapheresis in those with WBC counts greater than 60,000/µl. Methods: Allogeneic donors received 5 days of granulocyte colony‐stimulating factor (G‐CSF) at a daily dose of 10 or 16 µg/kg. Autologous donors received G‐CSF 10 µg/kg/day +/? chemotherapy until peripheral blood CD34⁺count reached 10/µl. Granulocyte donors received 300 µg dose of G‐CSF the day prior to donation. Results: Out of 3,037 leukapheresis collections from 1998 to 2005, we identified 303 collections from 204 donors or patients who had a WBC > 60,000/µl. WBC counts were ≥100,000/µl in seven of these subjects. If inadequate stem cell dose was obtained with pheresis with WBC counts this high, patients had growth factor dosing decreased 50% but still received a dose till stem cell collection was completed. Of the 204 subjects, 122 were patients and 82 were donors. These 204 donors/patients had no serious adverse events reported other than the common reports of myalgia, bone pain, and headache associated with administration of growth factors. Pain levels ranged from mild to severe and usually were managed by over the counter analgesics. Conclusions: Continuing ½ the dose of neupogen to complete the pheresis process appears safe in subjects with very high white blood counts. J. Clin. Apheresis 30:28–31, 2015. © 2014 Wiley Periodicals, Inc.     

Appropriate timing of G‐CSF use after mobilization chemotherapy significantly increases the yield of CD34+ cells in autoPBSCT

The yield of CD34+ cells collected by apheresis for autologous peripheral blood stem cell (PBSC) transplantation was greatly increased when the appropriate timing was determined to begin using G‐CSF after COAEP (Cytoxan, Vinblastine, Arabinosylcytosin, Etoposide and Prednisone) mobilization. Twenty‐nine patients with lymphoma or multiple myeloma (MM) received the same mobilization chemotherapy, including cytoxan (CTX) 400 mg/m² d1; vinblastine (VLB) 2 mg/m² d1; Ara‐C 60 mg/m² × 5d; vp‐16 60 mg/m² × 5d; and prednisone 40 mg/m² × 5d. The historical control group (12 cases) received subcutaneous G‐CSF (filgrastim) at the first restoration after the initial nadir of the peripheral WBC count. The experimental group (17 cases) received G‐CSF during the steady rise of the WBC count (end of fluctuating after initial nadir). G‐CSF was given in a single daily subcutaneous dose of 5 μg/kg until the final PBSC apheresis. When the peripheral WBC and mononuclear cell (MNC) counts reached 10 × 10⁹/L and 1 × 10⁹/L, respectively, leukapheresis was carried out using the COBE Spectrablood cell separator. Despite comparable treatment with alkylating agents, a significantly increased yield of CD34‐positive cells was observed in the experimental group (32 × 10⁶/kg) compared with the historical control group (3.1 × 10⁶/kg) (P = 0.0182). This result indicates the importance of appropriate timing for the use G‐CSF after mobilization chemotherapy to increase the CD34+ cell yield. J. Clin. Apheresis, 2009. © 2009 Wiley‐Liss, Inc.     

Mobilization of hemopoietic stem cells with high-dose methotrexate plus granulocyte-colony-stimulating factor in patients with primary central nervous system lymphoma

BACKGROUND: High‐dose therapy with autologous stem cell support after standard dose induction is a promising approach for therapy of primary central nervous system lymphoma (PCNSL). High‐dose methotrexate (HD‐MTX) is a standard drug for induction of PCNSL; however, data about the capacity of HD‐MTX plus granulocyte–colony‐stimulating factor (G‐CSF) to mobilize hemopoietic progenitors are lacking. STUDY DESIGN AND METHODS: This investigation describes the data from stem cell mobilization and apheresis procedures after one or two cycles of HD‐MTX for induction of PCNSL within the East German Study Group for Haematology and Oncology 053 trial. Eligible patients proceeded to high‐dose busulfan/thiotepa after induction therapy and mobilization. RESULTS: Data were available from nine patients with a median age of 58 years. The maximal CD34+ cell count per µL of blood after the first course of HD‐MTX was 13.89 (median). Determination was repeated in six patients after the second course with a significantly higher median CD34+ cell count of 33.69 per µL. Five patients required two apheresis procedures and in four patients a single procedure was sufficient. The total yield of CD34+ cells per kg of body weight harvested by one or two leukapheresis procedures was 6.60 × 10⁶ (median; range, 2.68 × 10⁶‐15.80 × 10⁶). The yield of CD34+ cells exceeded the commonly accepted lower threshold of 3 × 10⁶ cells per kg of body weight in eight of nine cases. Even in the ninth, hemopoietic recovery after stem cell reinfusion was rapid and safe. CONCLUSION: HD‐MTX plus G‐CSF is a powerful combination for stem cell mobilization in patients with PCNSL and permits safe conduction of time‐condensed and dose‐intense protocols with high‐dose therapy followed by stem cell reinfusion after HD‐MTX induction.     

母细胞型套细胞淋巴瘤的临床病理观察

目的 探讨母细胞型套细胞淋巴瘤（BV-MCL）的病理特征、免疫表型、诊断和鉴别诊断。方法 对2例BV-MCL行HE和免疫组化染色观察。结果 1例为经典型母细胞型，肿瘤细胞弥漫、中等偏大、染色质细，核分裂87个／10HPF；另1例为多形型母细胞型，肿瘤细胞弥漫、多形，中等大的细胞与大细胞混杂，核染色质粗，可见明显的核仁，核分裂36个／10 HPF。2例均cyclinD1（＋）。结论 BV-MCL少见，是MCL的一种变型，其病理形态和免疫表型特殊，需要与弥漫性大B细胞淋巴瘤、前驱B淋巴母细胞白血病／淋巴瘤等鉴别。     

Leukocytoreduction for acute leukemia.

Both in children and adults, acute leukemia may present with extremely high blast counts; a phenomenon known as hyperleukocytosis. Respiratory failure, intracranial bleeding, and severe metabolic abnormalities frequently occur in acute hyperleukocytic leukemias (AHLs) and are the primary determinants of the high early mortality (20% to 40%) observed. The process leading to these complications has long been known as leukostasis, but the biological mechanisms underlying its development and progression have remained unclear. Traditionally, leukostasis has been attributed to overcrowding of leukemic blasts in the microcirculation, and its treatment has focused on prompt leukocytoreduction. However, it is becoming increasingly evident that leukostasis results from the adhesive interactions between leukemic blasts and the endothelium; a mechanism that none of the current therapies directly addresses. The endothelial damage associated with leukostasis is likely to be mediated by cytokines released in situ and by subsequent migration of leukemic blasts in the perivascular space. The adhesion molecules displayed by the leukemic blasts and their chemotactic response to the cytokines in the vascular microenvironment are probably more important in causing leukostasis than the cell number. This may explain why leukostasis may develop in some patients with AHL and not in others, and why some patients with acute leukemia without hyperleukocytosis (<50,000 blasts/mm(3)) develop leukostasis and respond to leukocytoreduction. Leukapheresis effectively reduces the blast count in many patients with AHL and is routinely used for immediate leukocytoreduction. However, the most appropriate use of leukapheresis in acute leukemia remains unclear, and the procedure may not prevent early death more efficiently than fluid therapy, hydroxyurea, and prompt induction chemotherapy. The use of cranial irradiation remains very controversial and is not generally recommended. The identification of the adhesion molecules, soluble cytokines, and chemotactic ligand-receptor pairs mediating endothelial cell damage in AHL should become a priority if better outcomes are desired.     

The management of hyperleukocytosis in 2017: Do we still need leukapheresis?

Hyperleukocytosis is defined as a white blood cell count greater than 100.000/μL in patients affected by acute or chronic leukemias. Hyperleukocytosis is more common in acute leukemias than in chronic leukemias. Risk factors include younger age, acute myeloid leukemia, the microgranular variant of acute promyelocytic leukemia, acute lymphoblastic leukemia and some cytogenetic abnormalities. Although it can affect any organ system, symptoms usually arise from involvement of the cerebral, pulmonary and renal microvasculature. The term “leukostasis” refers to ‘symptomatic hyperleukocytosis’ which is a medical emergency that needs prompt recognition and initiation of therapy to prevent renal and respiratory failure or intracranial haemorrhage. The underlying mechanisms of hyperleukocytosis and leukostasis are poorly understood. The management of hyperleukocytosis and leukostasis involves supportive measures and reducing the number of circulating leukemic blast cells by induction chemotherapy, hydroxyurea, low-dose chemotherapy, and leukapheresis. The measures such as hydroxyurea, low-dose chemotherapy, and leukapheresis shouldn’t be considered to correct the laboratory abnormalities in patients with hyperleukocytosis who have no signs or symptoms. Also, neither hydroxyurea nore leukapheresis is able to show benefit on short and long term outcomes in patients with symptomatic hyperleukocytosis. The optimal management of symptomatic hyperleukocytosis is still uncertain, and there are no randomized studies demonstrating one is superior to each other. Therefore, it is recommended that intensive chemotherapy should be implemented as quickly as possible in treatment-eligible patients, in parallel with supportive measures for DIC and TLS.     

The management of hyperleukocytosis in an adult patient with acute lymphoblastic leukemia and ataxia-telangiectasia

Ataxia-telangiectasia (AT) is a hereditary disorder characterized by progressive neurological dysfunction, oculocutaneous telangiectasia, immunodeficiency, cancer susceptibility, and radiation sensitivity. Pediatric patients may develop acute lymphoblastic leukemia (ALL). However development of ALL in an adult patient with AT is a rare occurrence. Here we report such a patient who presented with hyperleukocytosis and were treated with leukapheresis. A 25 years old male patient, who were diagnosed with AT and mental retardation, was admitted to the emergency department due to fatigue, nausea and headache. On admission he had a moderate general condition and was fully cooperated. His white blood cell (WBC) count were 466 × 10⁹/l. Blastic cells were observed in peripheral blood smear. Flow cytometry (FC) of peripheral blood showed T-ALL. Two sessions of large volume leukapheresis was performed. Symptoms due to hyperleukocytosis markedly improved after leukapheresis. Patients with AT should be closely monitored due to risk of malignancy. Leukapheresis may improve the prognosis of high risk ALL patients presenting with hyperleukocytosis.     

Immune‐mediated pancytopenia induced by oxaliplatin: a case report

BACKGROUND: Drug‐induced immune pancytopenia is considered an uncommon disorder. CASE REPORT: A 76‐year‐old woman with metastatic gastric adenocarcinoma received 15 cycles of FOLFOX‐6 (oxaliplatin/folinic acid/fluorouracil) with a complete response. Upon disease progression, she was restarted on FOLFOX; during the seventh cycle of treatment, 1 hour after completing her oxaliplatin infusion, she presented oral bleeding, petechiae and generalized hematomas. Her platelet (PLT) count decreased from 164 × 10⁹/L to less than 5 × 10⁹/L within a 3‐hour period and her white blood cells (WBCs) decreased from 5 × 10⁹ to 1.5 × 10⁹/L. One day later she presented a decrease in hemoglobin level (from 11.4 to 10 g/dL, reaching 8.9 g/dL after 5 days). The patient's PLT and lymphocyte count started to recover after 3 days of immunosuppressive treatment. STUDY DESIGN AND METHODS: PLT, red blood cell (RBC), and WBC antibody detection tests were performed in the presence and absence of oxaliplatin. PLT‐associated antibodies were evaluated by monoclonal antibody immobilization of PLT antigen assay and flow cytometry; WBC antibodies were tested by flow cytometry; and RBC antibodies were evaluated by gel and indirect antiglobulin test tube testing drug‐treated RBCs and untreated RBCs in the presence of drug. RESULTS: Positive reactions were obtained only in the presence of the drug (1 mg/mL) for all tests performed (PLTs, RBCs, and WBCs). CONCLUSIONS: Our case convincingly demonstrates that oxaliplatin led to the production of drug‐dependent PLT, RBC, and WBC antibodies inducing pancytopenia in the patient. The oxaliplatin was discontinued and patient's hematologic values recovered to normal levels.     

Reducing costs in flow-cytometric counting of residual white blood cells in blood products: utilization of a single-platform bead-free flow-rate calibration method

BACKGROUND: Commercial flow‐cytometric methods for counting residual white blood cells (rWBCs) in leukoreduced blood products use calibration beads for estimation of the measured sample volume. A bead‐free flow‐rate calibration method is developed and validated. STUDY DESIGN AND METHODS: The analyzed volume was calculated by acquisition time (ACQ). Twenty‐nine spiking series of red blood cell (RBC) or platelet (PLT) products were prepared containing levels ranging from 0.08 × 10⁶ up to 2048 × 10⁶ WBCs/L. Nearly WBC‐free triple‐leukofiltered RBCs or PLT concentrates (PCs) served as background. Propidium iodide (PI) was used to identify rWBCs. Five RBC series were compared against a commercially available kit (LeukoSure, Beckman Coulter). Routine capabilities were tested on 41 RBC and 92 PC samples of two independent transfusion services. RESULTS: The lower detection limit in RBC was 0.08 × 10⁶ rWBCs/L for ACQ and 0.16 for LeukoSure. Criteria for linearity, accuracy, and precision were fulfilled within the range of 0.5 × 10⁶ to 512 × 10⁶ WBCs/L. For PCs, all these criteria were fulfilled between 0.5 × 10⁶ and 32 × 10⁶ rWBCs/L (lower detection limit of 0.25) for PI. ACQ and LeukoSure agreed sufficiently (81%) when tested on routine RBCs or PCs. CONCLUSION: A residual WBC count of fewer than 0.5 × 10⁶ WBCs/L can be accurately counted using the ACQ approach at a total reagent cost of less than 0.5€ per sample.     

Cyclophosphamide plus granulocyte‐colony stimulating factor for hematopoietic stem cell mobilization in patients with multiple myeloma

We retrospectively reviewed the results of cyclophosphamide (3 g/m²), doxorubicin and dexamethasone plus granulocyte‐colony stimulating factor (G‐CSF) (ID‐CY/DOX group), low‐dose cyclophosphamide (2 g/m²) plus G‐CSF (LD‐CY group) and G‐CSF alone (G‐CSF group) for stem cell mobilization in patients with multiple myeloma. A total of 89 patients with 93 mobilizations were included. Apheresis was started when total white blood cell (WBC) count >10 × 10⁹/L for ID‐CY/DOX and LD‐CY groups and after eight doses of G‐CSF (5 μg/kg twice daily) for G‐CSF group. For five mobilizations in ID‐CY/DOX group, the rate of successful mobilization (≥4.0 × 10⁶/kg CD34+ cells) was 80%. For 78 mobilizations in LD‐CY group, the successful rate was 80.8%. For 10 mobilizations in the G‐CSF group, the successful rate was 50%. The mean yield of CD34+ cells was higher in ID‐CY/DOX and LD‐CY groups as compared with that in G‐CSF group (P = 0.026 and 0.020, respectively). There was no difference in the yield of CD34+ cells between ID‐CY/DOX and LD‐CY groups (P = 0.831). After autologous stem cell transplantation, the days to neutrophil and platelet engraftment were similar in these three groups (P = 0.713 and 0.821, respectively). In conclusion, we observed that ID‐CY/DOX and LD‐CY plus G‐CSF for stem cell mobilization resulted in a higher successful rate and higher stem cell yields than G‐CSF alone and their engraftment time were similar. Total WBC count >10 × 10⁹/L can be used as a guide to start apheresis in CY‐based stem cell mobilization. J. Clin. Apheresis 31:423–428, 2016. © 2015 Wiley Periodicals, Inc.     

Leukapheresis do not improve early death rates in acute myeloid leukemia patients with hyperleukocytosis

Hyperleukocytosis (HL) is defined as the clinical condition when the white blood cell (WBC) count is above 100,000/mm³ in peripheral blood. It has been already shown in the literature that leukapheresis, a conventional technique to decrease the serum WBC level, is ineffective for long-term survival in cases of hyperleukocytotic acute myeloid leukemia (AML) with leukostasis. However, the effect of leukapheresis on early mortality is still unclear. In this study, we aimed to evaluate the effect of leukapheresis on early mortality of patients with AML who have HL. Twenty-eight de novo patients with AML, diagnosed with HL between 2002 and 2015 at the Hacettepe Hematology Department, were analyzed retrospectively. Leukapheresis was performed in 10 patients, and the mean WBC decrease with leukapheresis was 57.4 × 10³/μl which accounts for 31% of the initial WBC count. The indications for leukapheresis were hyperviscosity and prophylaxis in four and six patients, respectively. In the group of patients who received leukapheresis, three of four patients who had hyperviscosity symptoms died, and three of six patients died who did not have symptoms. In our study, we observed that the leukapheresis procedure is highly effective in reducing plasma WBC levels. However, although it is statistically insignificant, our findings also revealed that there is a much higher rate of death in patients who were treated with leukapheresis. Therefore we conclude that leukapheresis does not lower rates of early death; nevertheless, this finding should be confirmed by prospective studies with larger cohorts.     

Effectiveness and cost analysis of "just-in-time" salvage plerixafor administration in autologous transplant patients with poor stem cell mobilization kinetics

BACKGROUND: Plerixafor is a recently Food and Drug Administration (FDA)‐approved CXCR4 antagonist, which is combined with granulocyte–colony‐stimulating factor (G‐CSF) to facilitate stem cell mobilization of lymphoma and myeloma patients. STUDY DESIGN AND METHODS: To evaluate the effectiveness and the related costs of a “just‐in‐time” strategy of plerixafor administration, we performed a retrospective cohort study comparing 148 consecutive lymphoma and myeloma patients in whom mobilization was attempted during 2008 before the Food and Drug Administration (FDA) approval of plerixafor with 188 consecutive patients mobilized during 2009 after FDA approval. RESULTS: Plerixafor was administered to 64 of 188 patients considered to be at risk for mobilization failure due to either their medical history (“high risk,” n = 23) or the occurrence of peripheral blood CD34+ count of fewer than 15 × 10⁶ cells/L with a white blood cell count of greater than 10 × 10⁹ cells/L after at least 5 days of G‐CSF administration (just‐in‐time, n = 41). The success rates of collecting a minimum transplant CD34+ cell dose (≥2 × 10⁶ cells/kg) or target cell dose (≥5 × 10⁶ lymphoma or ≥10 × 10⁶ CD34+ cells/kg myeloma) in the just‐in‐time patients compared favorably with the 36 poor mobilizers collected with G‐CSF alone: 93% versus 72% and 42% versus 22%, respectively. CONCLUSIONS: The use of plerixafor in selected high‐risk patients and poor mobilizers did not increase the total charges associated with stem cell collection when compared with poor mobilizers treated with G‐CSF alone. The targeted use of plerixafor increased the overall success rate of mobilizing a minimum number of CD34+ cells from 93% to 98% in patients with hematologic malignancies scheduled for autotransplant and increased the overall charges associated with stem cell collection in all patients by an average of 17%.     

Leukopheresis for profound hyperleukocytosis

Background

Leukocytoreduction by leukopheresis is recommended for hyperleukocytosis with leukemia, especially when accompanied by neurologic or respiratory symptoms. A single 1-1.5 blood volume leukocytopheresis is expected to reduce the leukocyte count by 30-60%.

Case Report

A 35 year old man presented with a 2 month history of hearing and visual loss and was found to have chronic myelogenous leukemia (CML) in chronic phase with 700,000 WBC/μL. The blast count was 1%. The spleen was markedly enlarged. He was referred for leukocytopheresis and treatment of his leukemia. Despite the extremely high white cell count, he had a hematocrit of 24, platelets of 161,000/μL, and normal lung, liver and renal function.

Results

A 15 L leukocytapheresis was performed with a Cobe Spectra with the removal of 1.86 L of bloody fluid with a hematocrit of 10% and a leukocrit of 28%. The blood white cell count decreased from 599,000 to 498,500/μL, and the patient felt better. He was started on hydroxyuria and 8 days later his WBC was 7000/μL.

Discussion

The patient’s oncologists were initially concerned by the only 17% reduction in his white cell count. However, calculations based on his hematocrit and leukocrit in blood and waste bag suggested that he was 140% blood volume expanded by his leukemia and that the cytopheresis removed about half of the extra volume along with an additional 250 mL of leukocytes, about 35% of his pre-treatment WBC volume. The case and its implications for similar patients are discussed.     

Obtaining of CD34+ cells from healthy blood donors: development of a rapid and efficient procedure using leukoreduction filters

BACKGROUND: Human CD34+ cells are mandatory to study many aspects of human hematopoiesis. Their low frequency in blood or marrow and ethical reasons limit their obtainment in large quantities. Leukoreduction filters (LRFs) are discarded after preparation of red blood cells. The CD34+ cell concentration in healthy donor blood is low (1 × 10³‐4 × 10³/mL), but their number trapped in one LRF after filtration of 400 to 450 mL of blood is high (0.4 × 10⁶‐1.6 × 10⁶). STUDY DESIGN AND METHODS: To develop a procedure allowing obtainment of purified CD34+ cells from LRFs with a good yield, white blood cell (WBC) recoveries after a 500‐mL continuous or after sequential elution (50‐ or 20‐mL fractions) were compared. Different WBC and mononuclear cell (MNC) centrifugation methods were tested to minimize their PLT contamination before the CD34+ cell immunomagnetic selection. Cell functionality was finally analyzed under various culture conditions. RESULTS: The 20‐mL back‐flushing of LRFs allowed the most efficient WBC recovery. The next steps (110 × g centrifugation, MNC separation on Ficoll, and washes) resulted in a cell suspension in which the lymphocyte recovery was approximately 76 ± 10% and the PLT contamination below 1.6%. After immunomagnetic selection, 4 × 10⁵ to 6 × 10⁵ cells containing approximately 85% of functional CD34+ cells were obtained. CONCLUSION: This procedure allows the easy, rapid (<5 hr), and efficient preparation of large quantities of CD34+ cells having functional activities similar to those of CD34+ cells from other sources. Therefore, easily available and virally safe, LRFs represent an important and regular WBC source to work with human CD34+ cells, but also with other WBC types.