Hematopoeitic Stem Cell Transplantation Research Articles

Monitoring plasma voriconazole levels may prevent subtheraputic dosing in pediatric stem cell transplant (SCT) patients

7105 Background: Voriconazole is frequently used for prophylaxis and treatment of fungal infections during hematopoeitic stem cell transplant (SCT). Clinical studies demonstrate a poorer outcome when voriconazole concentrations are ≤0.5mcg/ml. Pediatric dosing schedules to achieve trough concentrations >0.5mcg/ml are not established. Methods: Retrospective analysis of voriconazole levels in 16 pediatric allogeneic SCT patients recieving fungal prophylaxis with oral or iv voriconazole. Ages ranged from 0.5 to 16 years, median 8 years. Serum levels were measured by high-performance liquid chromatography. Samples were obtained 5 to 7 days after start or change of voriconazole therapy. Ninety-eight total levels were evaluated. Results: Eight patients (50%) achieved a trough level > 0.5mcg/ml on the majority of samples tested at doses ranging from 3.5 to 10 mg/kg po q 12 hours. At constant dose there was a significant intra-patient variability in trough levels over time. Most patients failing to achieve adequate trough levels were below the median age (see table ). Changing to iv therapy in 3 patients with low trough levels after oral therapy did not improve the trough levels. Multi-time point measurements were > 0.5mcg/ml at 2 to 6 hours after oral dose, but fell to < 0.2mcg/ml by 12 hours in 3 patients tested. Of 98 voriconazole levels, 52 were ≤ 0.5mcg/ml and 74 were < 1.0 mcg/ml. Conclusions: Unlike reports in adult patients, we found that frequent monitoring of voriconazole levels was necessary in pediatric SCT patients due to intra-patient variability. Younger pediatric SCT patients may require more frequent dosing schedules to achieve trough levels. No significant financial relationships to disclose. [Table: see text]

Transplantation and Other Uses of Human Umbilical Cord Blood and Stem Cells

Human umbilical cord blood (CB) has established itself as a legitimate source for hematopoeitic stem cell transplantations. Since the first transplantation was performed in 1988, it is estimated that approximately 4,000 patients, with malignant and non-malignant diseases, were transplanted with CB. Comparing to bone marrow transplants, cord blood's collection is easier and safer. It is also quicker to perform CB transplantation from the time of beginning of donor search. One of the major advantages of it is the naïve nature of newborn's immune system. This allows transplantations with less restriction of the HLA system, and with fewer graft versus host disease (GVHD) cases. A true setback of CB transplantations is the slow pace of engraftment. This fact has negative impact on treatment related mortality and is related to the amount of stem cell infused. Since CB has limited nucleated cell dose, transplanting it to heavier patients, namely adults, poses many difficulties. But the skepticism about the possibility that CB might be used in adult hematopoetic stem cell transplantations, can decline after few large scale trials have shown that it is definitely a feasible procedure. Few fields of research might help to improve the outcome of CB transplantations. While some strategies are at different investigational stages, others are at advanced phases of clinical studies. Main strategies are based on expansion of the number of the stem cells in CB grafts, induction of a temporary engraftment with other stem cell sources, or reduction of the toxicity of the conditioning regimens. It is encouraging to witness that the outcome of CB transplantations is improving constantly. Other potential uses of CB are also discussed. It was used for gene transfer for primary immune deficiency, and it was also demonstrated in animal models that its stem cell could serve as regenerative cells in non-hematopoeitic injured tissues. CB has broad spectrum of possible uses, but hematopoeitic stem cell transplantation is still the major indication. In an era where 30-40% of patients will not have a matched related or unrelated donor, CB is a major alternative, which provide a true chance for cure for a wide variety of diseases.

Basic Theory and Clinical Applications of Flow Cytometry

Flow cytometry (FC) has become an important component in the diagnosis and monitoring of patients with a diverse array of diseases. While the basic principals underlying FC remain relatively unchanged, the technology and array of available reagents have continued to evolve, thus expanding the list of applications in laboratory medicine. This review provides an overview of the basic theory of FC including instrumentation, sample processing, and analysis. Additionally, current and future clinical applications of FC are discussed. Among these, applications of FC in solid organ and hematopoeitic stem-cell transplantation, transfusion medicine, hematopathology, and infectious diseases are presented. Finally, applications employed primarily in clinical research are presented in anticipation of their eventual use in the clinical laboratory setting.

213: Thrombotic complications: Etiology, treatment and outcome post-autologous and allogeneic hematopoeitic stem cell transplant. A single center experience

213: Thrombotic complications: Etiology, treatment and outcome post-autologous and allogeneic hematopoeitic stem cell transplant. A single center experience

Impact of CD31 mismatches on the outcome of hematopoeitic stem cell transplant of HLA-identical sibling

Graft-versus host disease (GVHD) complicating allogeneic hematopoeitic stem cell transplantation (HSCT) is often attributed to mismatching of minor histocompatibility antigens (mHags), which are poorly defined in humans. CD31 is a candidate human mHag relevant to acute GVHD (aGVHD), but reports disagree about its level of significance. Therefore, we examined the impact of CD31-matching on the outcome of HSCT in different hematological and immunological diseases. About 60 patients receiving HSC from their respective HLA-ABCDR and DQ-identical sibling were studied. DNA was used to study the CD31 allele polymorphism at the codon 125 (LL, LV or VV) in the patient-donor pairs using the principle of allele-specific PCR amplification. Four primer were used; two primers (forward and reverse) for the L allele and another two for the V allele.The CD31 identity was tested for correlation with HSCT outcome measures of aGVHD, chronic GVHD, and relapse. The gene frequency of CD31 alleles (LL, VV and LV) was 28.3, 20 and 51.7%, respectively. CD31 identity was found in 31 pairs (51.7%) versus 29 pairs (48.3%) for nonidentity. The CD31 noncompatibility showed statistical non-significant relation with aGVHD (G 0–I, and G II–IV) and chronic GVHD (De-novo and chronic on acute) (p = 0.59, p = 0.62, p = 036 and p = 0.83, respectively). The CD31 nonidentity had statistical significant relation with aGVHD versus no aGVHD (p = 0.008 and OR = 4.46). The CD31 nonidentity showed statistical significant relation with aGVHD (II–IV) versus no aGVHD (p = 0.012 and OR = 7.14) and also, aGVHD (0–I) versus the no aGVHD (p = 0.03, OR = 3.13, respectively). A statistical significant relation was found between CD31 nonidentity in patient-donor pairs and relapse (p = 0.014 and OR = 4.21).In conclusion, the donor-recipient CD31 nonidentity is a significant risk factor for aGVHD and relapse in HLA-identical sibling.

G-CSF(filgrastim) on day −1 (day before stem cell infusion) provides stable engraftment and good progression free and overall survival (PFS and OS) in hematopoeitic stem cell transplantation (HSCT)-Tata Memorial Centre experience

Background: Recombinant human G-CSF hastens neutrophil recovery following hematopoietic stem cell transplantation (HSCT), thus accelerating engraftment.The optimal timing for use of G-CSF in conjunction to HSCT needs to be established.We present our data on effects of adding an extra dose of G-CSF (filgrastim 5 micro gm/kg) on day -1 of HSCT. Patients and Methods: Forty three consecutive patients who underwent HSCT in one year period were given G-CSF on day +1 (day before stem cell infusion) in addition to the regular doses from day +1 till engraftment.

Microfluidic Device Allows Low-Cost Newborn Screening for Severe Combined Immune Deficiency (SCID)

RATIONALE: SCID is a group of life-threatening disorders characterized by extreme susceptibility to infection because of profound T cell failure. The incidence is around 1/100,000 live births; however, this figure underestimates the actual incidence because of infant deaths before diagnosis. Diagnosis is frequently delayed until the first serious infection around age 4-6 months. Unfortunately, newborn screening for SCID has not been possible because of the lack of a cost-effective test. Early diagnosis of SCID would improve survival by improving access to nutrition, antibiotics, intravenous immune globulin, and curative hematopoeitic stem cell transplantation.

Steroid Refractory Acute and Chronic Graft Versus Host Disease (GVHD) - Response to Photophoresis+/− Rituximab.

Acute GVHD is an important complication following hematopoeitic stem cell transplantation (HSCT), with significant attendant morbidity and mortality. High dose steroids remain the cornerstone of therapy. Steroid refractory GVHD carries a very poor prognosis. Various therapies are available for steroid refractory acute GVHD, but response is not uniform. Among the less intensive regimens, extracorporeal photopheresis (ECP) and rituximab, a chimeric humanized anti CD 20 monoclonal antibody have been shown to be useful in treating refractory acute and chronic GVHD. We describe 8 patients who developed GVHD following transplantation of HLA-identical stem cells, from siblings in 7 and from an unrelated donor in one. 2 patients had steroid refractory chronic GVHD of the liver, 3 patients had a refractory chronic GVHD of the skin and one had a steroid responsive restrictive pulmonary syndrome. Of the patients with skin GVHD, 2 had chronic scelrodermatous GVHD, which was of 20 years duration in one patient and 8 in the other. 2 patients had acute GVHD of the GI tract. The age range was 21– 53 years. All patients were in complete remission from their primary disease at the time of therapy for GVHD. 3 patients had a diagnosis of acute lymphoblasitc leukemia and 5 acute myeloid leukemia All had failed treatment with high dose steroids and/or tacrolimus and/or cellcept, and, one had also failed ATG therapy. Then therapy for refractory GVHD was initiated with rituximab in 3 patients and with photopheresis in 5. 7 patients received ECP. One patient with refractory chronic GVHD of the liver received rituximab alone in addition of steroids and tacrolimus. The patients with acute GVHD were treated with daily ECP for 10 days and then were weaned down to two procedures every 2 weeks. Patients with chronic GVHD received ECP 2 to 3 times a week for 6 weeks and were subsequently similarly weaned down. In the patients with acute GVHD of the GI tract complete responses occurred at 10 days in one patient and 45 days in the second as determined by complete cessation of diarrhea, cramps and nausea. Both patients with chronic GVHD of the liver achieved normalization of the serum bilirubin by 26 and 38 days after initiation of therapy. All patients tolerated successful taper of steroid therapy. The two patients with sclerodermatous GVHD have shown marked improvement in skin texture and range of motion at the involved joints. The patient with the pulmonary symptoms has shown complete normalization of pulmonary function. 5 patients were at risk of CMV reactivation, but failed to do so. One patient developed BK virus associated hemorrhagic cystitis that required therapy with cidofovir. There were 3 admissions for neutropenic fever, three for pneumonia and one each for gastroenteritis, HSV gingivostomatitis and line related sepsis. Two patients had line related thrombosis. None of the patients had relapse of their disease. 2 of the responders had an ECOG performance status 2, two of 3, one of 4 and four of </= 1 while being treated. All patients demonstrated improvement in functional status. ECP and rituximab is a well tolerated and effective modality for therapy of steroid refractory chronic and acute GVHD in both related and unrelated marrow stem cell transplant recipients.

Cord blood transplant in childhood ALL

Optimal therapy for high risk and relapsed acute lymphoblastic leukemia (ALL) remains uncertain. Wider availability of cord blood from related and unrelated donors has prompted studies of its use for hematopoietic stem cell transplant (HSCT). We evaluated 26 consecutive cord blood transplants (CBT) for ALL performed at our center from 1996 to 2002 on studies using consistent conditioning therapy and graft-versus-host disease (GVHD) prophylaxis. Median patient age was 8.5 years (range, 0.5-24 year). Cord blood (CB) was from unrelated donors in 25/26 cases. Median CB nucleated cell dose was 3.26e7/kg (range, 0.8-12.9). With median follow-up of 548 days, 16/26 patients (62%) are event-free survivors. Acute GVHD developed in 14/24 evaluable patients, reaching grade III-IV in 7 patients. Chronic GVHD occurred in 10/22 evaluable patients. Multivariate analysis showed higher total nucleated cell dose per kilogram to be the strongest predictor of event-free survival. We conclude that CBT can effectively treat ALL in children with high risk features and following relapse.

Hematopoietic Stem Cell Transplantation Phase III Clinical Trials for Patients with Hematological Malignancies in the US: Lessons To Be Learned from the European Experience.

Introduction: Evidence-based medicine defines standard therapies primarily from Phase III randomized controlled trials (RCT), when available. In this report we examined trends in ther number and characteristics of phase III RCT addressing the management of adult patients with hematological malignancies, comparing the patterns of activity in the US and Europe. Materials and Methods: We attempted to identify all phase III RCT published in the English medical literature from 1/1992 to 12/2003. A systematic search of Medline and published references was conducted using multiple keywords for each malignancy as well as for hematopoeitic stem cell transplant (HSCT). We cross-referenced the data by searching individual journals, as well as the ASH education books from 1998–2003. Studies published in abstract form only were not included. Results: We identified 306 published RCT that accrued a total of 4899 patients. Eighty-three of these studies included HSCT with a total accrual of 2081 patients. Country of origin included: US (n= 25), Europe (n=54), other (n=4). Four European countries (France, Italy, Germany and UK: FIGU) with a combined population similar to that of the US produced 32 studies. This figure for FIGU does not include their contributions to 12 separate European cooperative trials. There were no significant trends in the number of trials published per year during the study period. However, significant differences emerged when the focus of the studies and the accrual numbers were analyzed. RCTs comparing HSCT to standard dose therapy represented 34.9% of the 83 trials and 59.4% of FIGU trials, but only 4% (1 out of 25) of US studies (p &lt;.001). US trials accrued a mean of 110.2 patients per study, as compared to 205.3 in other countries and 222.6 in FIGU studies (p= .006). In multivariate analysis, only focus of study was independently related to greater study size (p&lt;.001). Among the remaining 223 trials not involving HSCT (US produced 68 and FIGU 77), a significant trend for increasing numbers of trials published per year during the study period was documented (p=.015). No significant differences in the mean number of patients accrued per trial (US= 279.5, other countries= 302.8 and FIGU= 347.8), or in the focus of the studies were observed in univariate or multivariate analysis. Conclusions: While there has been an increase in the number of Phase III RTCs in patients with hematological malignancies published during 1992–2003, the activity for HSCT trials has remained stationary. US HSCT trials have focused on issues other than the comparison of HSCT to standard therapies, such as graft manipulation, growth factors and graft versus host disease. US HSCT have accrued significantly fewer patients per study. The reasons for these differences are not apparent from our data, and may include patient and/or physician attitudes/biases toward phase III trials, issues of financial coverage for the HSCT procedure and/or health care delivery policies. There is a serious paucity of US trials defining the role of HSCT in the management of hematological malignancies.

Improved Outcomes of Autologous (Auto) Hematopoeitic Stem Cell Transplantation (HSCT) for Intermediate and High Risk (I/HR) Aggressive (AG) Non Hodgkin Lymphoma (NHL) with IV vs PO Busulfan (Bu) in a Bu, Cyclophosphamide (Cy) and Etoposide (E) Preparative Regimen.

The BUCYE preparative regimen was originally developed for allogeneic HSCT for advanced hematological malignancy (BMT 4:489-495). We have been using it as high dose chemotherapy for auto-HSCT for malignant lymphoma patients (pt). We have now had the opportunity to review the results of this experience in 49 I/HR AG NHL pt transplanted between 8/94 and 9/03. Eighteen pt treated before 4/99 received CY 2.5 Gm/M2/d d −3 to −1 and E 1800 mg/M2 over 4 hr on d −3 following BU 1mg/Kg Q6h X 16 doses administered po beginning on d −7. Since 4/99, 31 pt have received the same regimen substituting iv BU using Pharmacokinetics (PK) guided dosing to target an area under the concentration*time curve (AUC) of 1000–1400μMol *min on the same Q6h X 16 dose schedule. Eleven of these pt, treated prior to 3/01, had dose 8 adjusted based on dose1 PK and the remaining 20 had dose 1 or 2 adjusted based upon a test dose. We hypothesized that reduced inter- and intra-pt variation in AUC due to PK guided iv BU would reduce the risk of over or under treatment with excess risk of toxicity or relapse as compared to po administered drug. The age range (18–69, med 53 for po pt; 19–68, med 51 for iv pt), HR ratio (7/18, 39% for po pt; 14/31, 45% for iv pt), and number of prior chemotherapy regimens (1–3, med 2 for both) were the same for both the iv and po groups. The distribution of histological sub-classifications was also not different. The iv group consisted of 23 Diffuse Large B-Cell, 1 Burkitt, 2 Mantle Cell, 2 T cell and 3 others. The po group contained 16 Diffuse Large B-Cell, 2 Mantle Cell, 1 T cell and 4 others. The non-relapse mortality for the po BU pt was 5/13 (28%) and for the iv BU pt was 1/31 (3%) (p = 0.01 chi square). The overall survival (OS) for the po pt is currently 28% with no deaths beyond 4 yr and med follow up of survivors of 7 yr (range 4–10); in contrast the OS is 63% for the iv pt with no deaths beyond 2 yr and median follow up of survivors of 2 yr (range 4 mo to 4.5 yr), (p = 0.012 log rank). The progression free survival (PFS) is 22% for the po pt and 55% for the iv pt (p = 0.013 log rank). During the same time period we treated 48 Hodgkin's disease (HD) pt with the same regimen (17 po, 31 iv). There was no significant difference in any outcome parameter between iv and po regimens in this significantly younger (19–63 yr, med 31) and otherwise lower risk population. With follow up of survivors from 18 to 90 mo (med 36), OS is 60% at median follow up and PFS is 50%. Overall, the results of the use of the BUCYE regimen in auto HSCT for both HD and NHL are excellent. The substitution of PK guided iv BU for the more erratic po administration in the BUCYE regimen appeared to be responsible for reduced relapse rate and non-relapse mortality with improved OS and PFS. These results are especially dramatic in the I/HR AG NHL pt, the group at highest risk for relapse and regimen related mortality.

Safety of Low Dose Enoxaparin in Thrombocytopenic Hematopoeitic Stem Cell Recepients: A Single Institution'a Case Series.

When faced with a severely thrombocytopenic cancer patient with acute or chronic thrombus, oncologists often avoid antithrombotic treatment until the platelet count is above 50 x 109/L. Few attempts have been made to examine the feasibility of safely administering low-molecular-weight-heparins (LMWHs) in the presence of concurrent thrombocytopenia. We retrospectively investigated the safety of low-dose LMWH in hematopoeitic stem cell transplantation (HSCT) patients, a population at risk of bleeding. Our initial experience with the safe use of the LMWH enoxaparin in an HSCT patient published in 2002 (Annals of Pharmacotherapy 2002; 36:1478) was extended to 26 patients. Between August 2001 and August 2004, 26 HSCTs patient received at least one dose of enoxaparin during thrombocytopenia. Patients'baseline characteristics are shown below.Table 1. Baseline characteristics of the study patients (n=26)Two patients received enoxaparin twice during 2 successive thrombocytopenic periods, thereby accounting for 28 safety evaluations. Subcutaneous enoxaparin 40 mg once daily was given in 85% (22/26) of the cohort. Minor bleeding occurred in 4 patients (15%) whereas major episodes developed in 2 patients (8%). These two patients experienced retroperitoneal bleeding during the transition full/low- dose anticoagulation. Dose/platelet count at the time of bleeding were: 2.35 mg/kg/d and 81 x 109/L, and 1.15 mg/kg/d and 52 x 109/L in the first and second patient respectively. The latter patient had an elevated serum creatinine at 2 mg/dl. The mean number of platelets days < 55 x 109/L and < 20 x 109/L were 16.5 days (95% CI=8.04–24.96) and 4.14 days (95% CI=2.35–5.93) respectively. The mean number of platelet transfusion was 4.93 (95% CI=2.65–7.21). The mean number of low-dose enoxaparin administration days when platelet < 55x 109/L and 20 x 109/L were 9.89 days (95% CI= 3.26–16.53) and 2.25 days (95%CI=0.57–3.93) respectively. The mean number of enoxaparin interruptions during thrombocytopenia was 2.75 days (95%CI=1.11–4.39). During thrombocytopenia, the median 4-hour post-dose anti-Xa level was 0.28 units/ml (range:0.04–0.4 units/ml; n=5). The present case series descriptively suggests that low-dose enoxaparin may be safely administered platelet count in the range of 20–55 x 109/L in HSCT patients who weigh > 55 Kg. The safety of low-dose LMWHs below 20 x 109/L remains to be established. Importantly, the transition from/to low-dose enoxaparin should be done at a higher platelet count threshold than 55 x 109/L, all the more in the presence of compromised renal function.Table 1. Baseline characteristics of the study patients (n=26)Age (median; range)53 years (24–67)Gender (M/F)17/9Weight (median; range)83.4 Kg (53–176)Type of HSCT¹Autologous (20), Allogeneic (2), non-myeloablative (3), cyclophosphamide priming (3)Thrombotic event²upper extremity DVT (11), lower extremity DVT (9), pulmonary embolism (5), miscellaneous events (5)Number of patients on full-dose enoxaparin prior to thrombocytopenia (%)14 (54%)Indications for HSCTmultiple myeloma (10), lymphoma (9), leukemia (2), breast cancer (2), miscellaneous indications (3)Two patients received enoxaparin during 2 successive thrombocytopenic periods ¹, 2 patients had upper and lower extremity DVT, 2 patients had lower extremity DVT and pulmonary embolism²Age (median; range)53 years (24–67)Gender (M/F)17/9Weight (median; range)83.4 Kg (53–176)Type of HSCT¹Autologous (20), Allogeneic (2), non-myeloablative (3), cyclophosphamide priming (3)Thrombotic event²upper extremity DVT (11), lower extremity DVT (9), pulmonary embolism (5), miscellaneous events (5)Number of patients on full-dose enoxaparin prior to thrombocytopenia (%)14 (54%)Indications for HSCTmultiple myeloma (10), lymphoma (9), leukemia (2), breast cancer (2), miscellaneous indications (3)Two patients received enoxaparin during 2 successive thrombocytopenic periods ¹, 2 patients had upper and lower extremity DVT, 2 patients had lower extremity DVT and pulmonary embolism²

Effect and Kinetics of Depleting ACK-2 Anti C-Kit Monoclonal Antibody on Hematopoeisis and Hematopoetic Progenitors and Ability To Condition for Bone Marrow Transplantation.

c-kit is expressed on hematopoetic stem and progenitor cell populations. ACK-2 is an anti-mouse c-Kit monoclonal antibody which has been shown (by Nishikawa et al) to antagonize the function of c-kit and deplete the bone marrow of treated mice. We wished to characterize the effect of the anti c-kit mAb ACK-2 on the peripheral blood cell counts and marrow hematopoetic stem cell and progenitor populations. We also tested the hypothesis that treatment with ACK-2 may serve as a novel means of non-myeloablative conditioning for hematopoeitic stem cell transplantation. METHODS: Adult C57 black mice were injected either intravenouslyl or intraperitonealy with 1mg of ACK2 mAb every other day on Day 0, Day 2 and Day 4. Peripheral blood cell counts, including white cell differentials were followed over time in recipient mice. Peripheral blood and bone marrow was analyzed at Day 7, and marrow was analyzed for fraction and proportions of hematopoetic stem cells (HSC), common myeloid progenitors (CMP), granulocyte macrophage progenitors (GMP) and macrophage erythrocyte progenitors (MEP). A subset of Ly5.1 mice which had received ACK2 mAb on Days 0,2 and 4 received a bone marrow transplant on Day 7 with 1 Million bone marrow cells from a Ly5.2 donor. Peripheral blood from transplanted recipient mice was analyzed three weeks post transplant for presence of Ly5.2 donor derived cell engraftment. RESULTS: Both intravenous and intraperitoneal administration of ACK-2 resulted in rapid development of anemia, neutropenia and thrombocytopenia. In mice treated with intravenous ACK-2 on Days 0,2,4, the WBC dropped from a mean (3 mice) of 12.12 at Day 0 in untreated controls, to 6.6 at Day 2 to 4.2 at Day 4, and to 2.56 at day 7, recovering to a WBC of 9.5 by Day 11. The mean neutrophil dropped rapidly from a control mean of 796 prior to treatment, to 180 at Day 2, to 32 on Day 4, 26 on Day 7, recovering to a mean of 320 by Day 11. Hemoglobin dropped from a pretreatment mean of 15.1 to 14.5, 13.2, 6.2 and 5.3 on Days 2,4,7,11 respectively. Platelet counts fell from 1107 pre ACK-2 to 763 at Day 7 and 220 and Day 11, recovering to 1226 by Day 16. Analysis of Day 7 peripheral blood revealed an decrease in Mac-1+ cells from 12.2 of circulating white cells in untreated controls to 3.1%, while the proportion of B220+ B cells increased from 49.7 to 72.7%. The fraction of circulating T cells decreased from 24.5% to 11.1% at Day 7. The bone marrow fraction of KTLS HSC decreased from.07% in controls to.003% in Day 7 treated mice. Marrow fraction CMP decreased from 12% in untreated to 4.7% in treated, wheras the GMP population dropped from 66 to 53%. In ACK-2 treated mice which received 1 Million Ly5.2 syngeneic bone marrow cells analyzed at Day 21 post transplant, there was no evidence of Ly5.2+ donor derived peripheral blood white cells, as compared to 80% Ly5.2 donor derived cells in control mice which had received 9 Gray of radiation for conditioning. CONCLUSIONS: The anti-kit Monocolonal antibody rapidly induces anemia, neutropenia and thrombocytopenia with decreases in the marrow HSC and other progenitor populations. ACK-2 does not appear to facilitate non-myelablative conditioning for a syngeneic graft when given alone.

Stem Cells: Current Usage and Future Potentials

In recent years, the term “haematopoeitic stem cell transplantation” has replaced “bone marrow transplantation”. It is more precise and emphasises the “haematopoeitic stem cell” as the key element.

Treatment strategies in childhood cancer

Strategies for the treatment of childhood cancer have significantly evolved over time. Years ago, surgery was the only option for treating childhood cancer. Now, research has advanced treatment options to include multimodal therapy with chemotherapy, radiation, surgery and hematopoeitic stem cell transplantation. The focus on gene therapy research is also increasing. Pediatric nurses must have a thorough understanding of the treatment for childhood cancer so that as frontline healthcare providers, they give accurate information to patients and their families, deliver appropriate care, and assist with gathering data in support of ongoing research. Copyright 2003, Elsevier Inc. All rights reserved.

Reconstitution of T-cell repertoire after autologous stem cell transplantation: influence of CD34 selection and cytomegalovirus infection.

The period of immunodeficiency following autologous hematopoietic stem cell transplantation is characterized by transient expansions of CD8+CD45RO+CD57+ T lymphocytes, displaying markers of an activated phenotype. Most evidence suggests that this early reconstitution results from proliferation of mature T cells that have survived conditioning or were transferred with the graft. Although homeostatic mechanisms are thought to act in maintaining total T-cell numbers, the degree to which antigen-driven expansions contribute and the nature of the stimulating antigens remain unclear. CD34 selection of stem cell grafts reduces the available T-cell pool, potentially delaying immune reconstitution and resulting in increased infective complications. In the allogeneic transplantation setting, lymphopenia has been associated with cytomegalovirus (CMV) infection risk and, if persistent, with adverse outcome. We prospectively studied patients undergoing CD34-selected (n = 13) or unselected (n = 13) autologous hematopoeitic stem cell transplantation for immune reconstitution and CMV infection. No significant differences were demonstrated between graft types with respect to lymphocyte subset recovery, T-cell receptor beta-chain variable region spectratype diversity, or CMV DNA detection rates (45% versus 40%). CMV infection was associated with a trend toward higher rather than lower CD8+ counts at 6 weeks posttransplantation (P =.08) that became significant by 3 months (P=.007), and that was associated with decreased T-cell receptor beta-chain variable region spectratype diversity (P =.01). CMV-specific HLA-tetramer analysis demonstrated transient expansions with CDR3 lengths corresponding to those of some of the major posttransplantation T-cell expansions demonstrated by spectratype analysis suggesting that CMV-specific T cells contribute to the pattern of immune reconstitution.

Reconstitution of T-cell repertoire after autologous stem cell transplantation: Influence of CD34 selection and cytomegalovirus infection

The period of immunodeficiency following autologous hematopoietic stem cell transplantation is characterized by transient expansions of CD8+CD45RO+CD57+ T lymphocytes, displaying markers of an activated phenotype. Most evidence suggests that this early reconstitution results from proliferation of mature T cells that have survived conditioning or were transferred with the graft. Although homeostatic mechanisms are thought to act in maintaining total T-cell numbers, the degree to which antigen-driven expansions contribute and the nature of the stimulating antigens remain unclear. CD34 selection of stem cell grafts reduces the available T-cell pool, potentially delaying immune reconstitution and resulting in increased infective complications. In the allogeneic transplantation setting, lymphopenia has been associated with cytomegalovirus (CMV) infection risk and, if persistent, with adverse outcome. We prospectively studied patients undergoing CD34-selected (n = 13) or unselected (n = 13) autologous hematopoeitic stem cell transplantation for immune reconstitution and CMV infection. No significant differences were demonstrated between graft types with respect to lymphocyte subset recovery, T-cell receptor β-chain variable region spectratype diversity, or CMV DNA detection rates (45% versus 40%). CMV infection was associated with a trend toward higher rather than lower CD8+ counts at 6 weeks posttransplantation ( P = .08) that became significant by 3 months ( P= .007), and that was associated with decreased T-cell receptor β-chain variable region spectratype diversity ( P = .01). CMV-specific HLA-tetramer analysis demonstrated transient expansions with CDR3 lengths corresponding to those of some of the major posttransplantation T-cell expansions demonstrated by spectratype analysis suggesting that CMV-specific T cells contribute to the pattern of immune reconstitution. © 2003 American Society for Blood and Marrow Transplantation Biology of Blood and Marrow Transplantation 9:198-205 (2003)

Diagnostic methodologies for invasive fungal infections in hematopoietic stem-cell transplant recipients.

Hematopoeitic stem cell transplantation (HSCT) is now a well-established treatment modality for a variety of solid tumors and hematologic malignancies. However, pulmonary complications, especially invasive fungal infections, are still a major cause of morbidity and mortality in this population. Successful management of invasive fungal infection depends on early diagnosis, prompt initiation of appropriate anti-fungal therapy, and return of immuno-competence. Appropriate timing of imaging studies and the use of invasive procedures can be lifesaving. Newly developed noninvasive diagnostic techniques allow for earlier recognition of fungal infection and hence earlier treatment. Identifying patients at risk for fungal infections (ie, prolonged neutropenia), and when infection is suspected, using appropriate diagnostic modalities, leads to effective prophylactic and earlier empiric therapy.

Bone marrow necrosis associated with relapse of acute myelogenous leukemia following unrelated hematopoeitic stem cell transplantation using an immunoablative regimen

Medical and Pediatric OncologyVolume 38, Issue 2 p. 148-149 Letter to the Editor Bone marrow necrosis associated with relapse of acute myelogenous leukemia following unrelated hematopoeitic stem cell transplantation using an immunoablative regimen Lakshmi Venkateswaran MD, Corresponding Author Lakshmi Venkateswaran MD lakshmimd@hotmail.com Department of Stem Cell Transplantation Program, Children's Memorial Hospital, Chicago, IllinoisDepartment of Stem Cell Transplantation Program, Children's Memorial Hospital, Chicago, Illinois.Search for more papers by this authorReggie Duerst MD, Reggie Duerst MD Department of Pediatrics and Department of Stem Cell Transplantation Program, Children' Memorial Hospital, Chicago, IllinoisSearch for more papers by this authorPaul Haut MD, Paul Haut MD Department of Pediatrics and Department of Stem Cell Transplantation Program, Children' Memorial Hospital, Chicago, IllinoisSearch for more papers by this authorMorris Kletzel MD, Morris Kletzel MD Department of Pediatrics and Department of Stem Cell Transplantation Program, Children' Memorial Hospital, Chicago, IllinoisSearch for more papers by this authorPauline Chou MD, Pauline Chou MD Department of Pathology, Children's Memorial Hospital, Chicago, IllinoisSearch for more papers by this author Lakshmi Venkateswaran MD, Corresponding Author Lakshmi Venkateswaran MD lakshmimd@hotmail.com Department of Stem Cell Transplantation Program, Children's Memorial Hospital, Chicago, IllinoisDepartment of Stem Cell Transplantation Program, Children's Memorial Hospital, Chicago, Illinois.Search for more papers by this authorReggie Duerst MD, Reggie Duerst MD Department of Pediatrics and Department of Stem Cell Transplantation Program, Children' Memorial Hospital, Chicago, IllinoisSearch for more papers by this authorPaul Haut MD, Paul Haut MD Department of Pediatrics and Department of Stem Cell Transplantation Program, Children' Memorial Hospital, Chicago, IllinoisSearch for more papers by this authorMorris Kletzel MD, Morris Kletzel MD Department of Pediatrics and Department of Stem Cell Transplantation Program, Children' Memorial Hospital, Chicago, IllinoisSearch for more papers by this authorPauline Chou MD, Pauline Chou MD Department of Pathology, Children's Memorial Hospital, Chicago, IllinoisSearch for more papers by this author First published: 21 January 2002 https://doi.org/10.1002/mpo.1299Citations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume38, Issue2February 2002Pages 148-149 RelatedInformation