Lung transplant after 6 months on ECMO support for SARS-CoV-2-induced ARDS complicated by severe antibody-mediated rejection

There have been a few reports of successful lung transplantation (LTx) in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS); however, all reports were with rather short follow-up. Here we present a 62-year-old man without prior lung diseases. Following SARS-CoV-2-induced ARDS and 6 months of extracorporeal membrane oxygenation, he underwent LTx. 3 months post-transplantation he developed acute hypoxia requiring emergency intubation. Chest imaging showed acute rejection, and de novo DQ8-DSA was discovered. He was treated with a high dose of corticosteroids and plasmapheresis and was extubated 4 days later, yet the de novo DQ8-DSA remained. After sessions of plasmapheresis and rituximab, the levels of de novo DQ8-DSA remained unchanged. Nine months post-transplantation the patient died of respiratory failure. We herein discuss the decision to transplant, the transplantation itself and the postoperative course with severe antibody-mediated rejection. In addition, we evaluated the histological changes of the explanted lungs and compared these with end-stage idiopathic pulmonary fibrosis tissue, where both similarities and differences are seen. With the current case experience, one might consider close monitoring regarding DSA, and gives further support that LTx should only be considered for very carefully selected patients.

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A case report on lipofuscin deposition in a graft biopsy two years after kidney transplantation: an insignificant bystander or a pathogenic benefactor?

BMC Nephrology ◽

10.1186/s12882-019-1569-6 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Vivian W. Y. Leung ◽

Sarah-Jeanne Pilon ◽

Pierre O. Fiset ◽

Shaifali Sandal

Keyword(s):

Medical History ◽

Kidney Transplant ◽

Graft Function ◽

High Dose ◽

Solid Organ ◽

Past Medical History ◽

Post Transplantation ◽

Genetic Syndrome ◽

Antibody Mediated Rejection

Abstract Background Lipofuscin deposition is a characteristic manifestation of aging. There is very limited literature in humans and in animals describing these deposits in native kidneys. Overall, it is thought to be non-pathogenic and successful transplants from a donor with lipofuscin deposits have been reported. We present the case of a patient who underwent a kidney transplant and a for-cause biopsy post-transplantation incidentally revealed lipofuscin deposition. Case presentation A 48-year old gentleman with a past medical history of diabetes, hypertension, coronary artery disease, and ischemic and then hemorrhagic cardiovascular accident underwent a successful kidney transplant. His donor was an expanded criteria donor with no major past medical history. Post-transplant course was complicated by delayed graft function requiring one dialysis treatment for hyperkalemia. After that he had an uneventful course and achieved a baseline creatinine of 1.2 mg/dL, with no proteinuria. On a routine 19-month follow-up he was noted to have proteinuria and an antibody against the major-histocompatibility-complex class I-related chain A. A graft biopsy revealed acute antibody-mediated rejection and impressive lipofuscin deposition. He was subsequently treated with an antibody-mediated rejection protocol that included high dose steroids, Rituximab, plasmapheresis, and intravenous immunoglobulin, but responded poorly to this regimen. A 6-month follow up biopsy continued to show lipofuscin deposition, with similar microvascular injury scores and 12-months later his creatinine remained stable but his proteinuria worsened. Patient was struggling with recurrent infectious episodes requiring hospitalizations and thus no further diagnostic or therapeutic treatments were pursued. Conclusions Lipofuscin deposition has been reported in solid organ transplants but the significance and cause are not well understood. Several physiologic and some pathologic causes to these deposits have been reported including age, diabetes, medications and a genetic syndrome. We propose that immunologic causes such as rejection in the presence of other risk factors could potentiate the oxidative stress leading to excessive lipofuscin deposition in kidney transplants. In the case of our patient, we conclude that these deposits were likely recipient-derived, and postulate that the cumulative burden of inflammation from rejection, and underlying medical conditions led to increased lipofuscin deposition. We speculate them to be an innocent bystander.

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MO960RENAL TRANSPLANTATION FROM A LIVING DONOR WITH RENAL ARTERY FIBROMUSCULAR DYSPLASIA

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab110.0039 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Eva Paraskevi Andronikidi ◽

Glykeria Tsouka ◽

Myrto Giannopoulou ◽

Konstantinos Botsakis ◽

Xanthi Benia ◽

...

Keyword(s):

Renal Disease ◽

Serum Creatinine ◽

Renal Artery ◽

Left Renal Artery ◽

Close Monitoring ◽

History Of ◽

The Right ◽

Stage Renal Disease ◽

End Stage

Abstract Background and Aims Renal transplantation is considered the most effective and less costly modality of renal replacement therapy in patients with end stage renal disease. The disparity between kidney allografts and recipients has led to a global effort to increase the pool of kidney donors. Accordingly, fibromuscular dysplasia (FMD) is no longer considered an absolute contraindication for kidney donation. The incidence of FMD is about 2.3%-5.8% in potential kidney donors. There are few cases in the literature where renal artery stenosis in allografts with known pre-transplantation FMD became worse after transplantation, indicating the importance of a proper follow up in the recipients. This is a case of a living kidney donor with no history of hypertension, proteinuria or elevated serum creatinine, whose intra-arterial digital subtraction angiography revealed FMD lesions in the left renal artery. Method Case report Results A 54-year-old Caucasian female with medical history of hypothyroidism took the decision to offer her kidney to her 37-year-old son who was diagnosed with end-stage renal disease five years ago secondary to diabetes mellitus type I. She had no history for diabetes, hypertension and renal disease. Her vital signs on admission were heart rate of 78 beats/min and blood pressure of 130/70 mmHg. Urinalysis, biochemical profile and serological evaluations were all within normal ranges. Blood urea was 36 mg/dL and serum creatinine was 0.6 mg/dL (eGFR 97ml/min/1.73m2). The abdominal ultrasound and renogram with Tc-99m DTPA showed no remarkable findings. On intra-arterial digital subtraction angiography an abnormal succession of dilatations and multifocal stenoses of the left renal artery, characteristic of medial FMD, was found. The right renal artery was normal. Apart from a dysfunctional permanent left femoral catheter, the patient had no other vascular access for hemodialysis because of Superior Vena Cava syndrome, so he needed urgent transplantation. Taking all of these into consideration, the patient was offered renal transplantation as the best option. A left open donor nephrectomy was performed; the renal artery was divided distal to the stenotic dysplastic area. The allograft was placed at the right iliac fossa of the recipient with arterial and venous anastomosis to the extrarenal iliac vessels. Post-operatively, the recipient had a delayed graft function lasted 13 days. On renal artery Doppler in the allograft we found increased resistance index (RI) that gradually normalized without any intervention. An immunosuppressive regiment of tacrolimus, mycophenolate and prednisone was administered according to our center protocol. At discharge serum creatinine was 1.7 mg/dL (eGFR: 50ml/min/1.73m2). At the year follow-up, the donor was normotensive and had near normal renal function (Cr:1.3mg/dL, eGFR: 70ml/min/1.73m2). The recipient has a well-controlled blood pressure receiving two antihypertensive drugs and maintains a satisfactory renal function. Conclusion Few cases with FMD in renal allografts from living and deceased donors have been described. In a review of 4 studies the authors concluded that the outcome of transplantation with allografts from living donors with medial FMD was satisfactory and these allografts could be used to increase the donor pool. Furthermore, it is strongly recommended to have a thorough pre-transplantation check of the donor as well as a close monitoring of both the donor and recipient after transplantation. This case shows that allografts harvested from carefully selected donors with renal arterial FMD can be successfully used, particularly in urgent conditions. Detailed pre-tranplantation imaging of donor’s renal arteries, selection of the appropriate screening method, as well as close monitoring of both donor and recipient for early interventions after transplantation is of paramount importance.

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Antibody-mediated rejection with detection of de novo donor-specific anti-human leucocyte antigen Class II antibodies 3 years after heart transplantation: a case report

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytz246 ◽

2020 ◽

Vol 4 (1) ◽

pp. 1-4

Author(s):

Bernd Ludwig ◽

Johanna Schneider ◽

Daniela Föll ◽

Qian Zhou

Keyword(s):

Heart Transplantation ◽

De Novo ◽

Survival Rates ◽

Graft Function ◽

Left Ventricular ◽

Cardiac Allograft ◽

Left Ventricular Ejection ◽

High Dose ◽

Ventricular Ejection Fraction ◽

Antibody Mediated Rejection

Abstract Background Antibody-mediated rejection (AMR) in cardiac transplantation may manifest early within the first weeks after transplantation but also late after months to years following transplantation resulting in mild heart failure to cardiogenic shock. While patients with early cardiac AMR are less affected and seem to have survival rates comparable to transplant recipients without AMR, late cardiac AMR is frequently associated with graft dysfunction, fulminant forms of cardiac allograft vasculopathy, and a high mortality rate. Nevertheless, AMR of cardiac allografts remains difficult to diagnose and to treat. Case summary We report the case of a 47-year-old male patient with late AMR of the cardiac allograft 3 years after heart transplantation. Antibody-mediated rejection was confirmed by endomyocardial biopsy and the presence of donor-specific antibodies (DSA). The patient was treated with high dose of prednisolone, plasmapheresis, intravenous Gamma Globulin, rituximab, immunoadsorption, and bortezomib. Under this treatment regimen left ventricular ejection fraction and pro B-type natriuretic peptide recovered, and the patient improved to New York Heart Association Class I. Currently, 3 years after the diagnosis of cardiac AMR, graft function continues to be nearly normal, and there is no evidence for transplant vasculopathy. Discussion This case illustrates that AMR can occur at any time after transplantation. Although graft function fully recovered after treatment in our patient, the level of DSA remained high, suggesting that DSA may not be a reliable parameter to determine the intensity and duration of the therapy.

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Outcomes in CCG-2961, a Children’s Cancer Group Phase III Trial for Untreated Acute Myeloid Leukemia (AML).

Blood ◽

10.1182/blood.v106.11.169.169 ◽

2005 ◽

Vol 106 (11) ◽

pp. 169-169 ◽

Cited By ~ 2

Author(s):

Beverly J. Lange ◽

Franklin O. Smith ◽

Patricia A. Dinndorf ◽

Carola A.S. Arndt ◽

Dorothy R. Barnard ◽

...

Keyword(s):

De Novo ◽

Interleukin 2 ◽

Disease Free Survival ◽

Phase Iii ◽

Remission Induction ◽

High Dose ◽

Free Survival ◽

Cancer Group ◽

De Novo Aml

Abstract CCG-2961 tested an intensively timed induction therapy consisting of cytarabine (AC), etoposide, thioguanine, dexamethasone, idarubicin and daunorubicin. Patients in remission after induction were randomized to a second induction course (Arm A) or a 3-drug combination of fludarabine, AC, and idarubicin (Arm B). Course 3 for patients with related donors was bone marrow transplantation (BMT); for those without donors, high dose AC/l-asparaginase. After Course 3 patients without donors were randomized to 14 infusions of Interleukin 2 (IL2) over 18 days or follow-up. CNS prophylaxis was intrathecal AC. Eligibility included all subtypes of de novo AML except acute promyelocytic leukemia and AML in patients with Down syndrome. CCG-2961 opened in Oct.1996 and closed in Dec. 2002. The DSMC suspended the study between Oct. 1999 and May 2000 while the 2961 Committee developed supportive care policies to reduce treatment-related mortality (TRM). CCG-2961 enrolled 900 de novo patients aged 3 days to 21 years, with 495 and 405 patients accruing pre-and post suspension respectively. Remission induction rate is 88.5%. With median follow-up of 3.6 years (range: 0 – 8.1 years), event-free survival (EFS) at 3 years is 44±3% and survival (OS) 57±3%. Disease-free survival (DFS) following Course 2 Arms A and B are not different, although relapse is significantly higher in Arm A (7.3% .vs. 3.1% P=0.018) and TRM more common in Arm B (7.9% vs.4.2% P=0.059), despite 7 less days of neutropenia in Arm B (P<0.001). DFS is 65±9% for patients with a donor versus 50±5% for patients without a donor (P=0.005); respective OS, 74±8% and 66±5% (P=0.221). However, among 98 patients in CR1 with t(8;21) or inv(16) cytogenetics, outcomes in those without and with a donor were no different: DFS (61±12% vs. 72±18%, P = 0.49) and OS (78±10% vs. 77±17%, l P= 0.85). DFS with and without IL2 is 55±9% and 60±8%(P=0.606). Outcomes improved progressively over time. EFS pre- and post-suspension are 41±4% and 47±5%(P=0.038); OS, 52±5% and 63±5%(P=0.005); TRM is 17±3% pre- and 12±3% post-suspension (P=0.039). Factors predictive of inferior EFS are age >17 years, Afro-American and Hispanic ethnicity, body mass index <10th or >95th percentile for age, absence of related marrow donor, WBC > 50,000/mm3, karyotype with −7/7q, −5/5q- or > cytogenetic 5 abnormalities, FLT3/ITD, >15 % morphologic blasts on day 14 or >0.5% immunologically detectable blasts at the end of induction. CCG-2961 confirms the efficacy and high TRM of intensively timed therapy. Neither fludarabine nor IL2 increases DFS or OS, and availability of a donor does not improve outcomes in those with favorable cytogenetics.

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Post-Transplantation High-Dose Cyclophosphamide (Cy) Is Effective Single Agent GVHD Prophylaxis That Permits Prompt Immune Reconstitution after Myeloablative HLA Matched Related and Unrelated Bone Marrow Transplantation (BMT).

Blood ◽

10.1182/blood.v108.11.2891.2891 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2891-2891 ◽

Cited By ~ 1

Author(s):

Luznik Leo ◽

Chen R. Allen ◽

Kaup Michele ◽

Bright C. Emilie ◽

Bolanos-Meade Javier ◽

...

Keyword(s):

T Cells ◽

Chronic Gvhd ◽

Single Agent ◽

High Dose ◽

Post Transplantation ◽

Cell Counts ◽

Gvhd Prophylaxis ◽

Grade Ii ◽

The Impact

Abstract Prolonged pharmacologic immunosuppression is a major obstacle to early immunologic recovery after allogeneic BMT. Based on our results in animal models, we studied whether properly timed high-dose Cy post-HLA matched related and unrelated BMT is an effective strategy for limiting GVHD; we hypothesized that avoiding prolonged immunosuppression would speed immune recovery and reconstitution of regulatory T cells (T regs) thereby decreasing post-transplant complications. We are reporting results on 46 consecutive patients (median age 41, range 1–64) with high-risk hematologic malignancies (20 AML, 12 ALL, 6 NHL, 3 HD, 2 MM, 2 CML, 1 CMMoL); 28 received related and 18 unrelated unmanipulated HLA-matched BM (median of 2.2 x 108 MNC per kg) after conditioning with busulfan on days -7 to -3 and Cy (50 mg/kg/day) on days -2 and -1, and followed by Cy (50 mg/kg/day) on days +3 and +4 as the sole GVHD prophylaxis. All the patients had advanced disease (20 in advanced remission with the rest having refractory disease), and the median follow-up is 13 (range 6–24) months. All but two patients had sustained engraftment. The cumulative incidence of acute grades II–IV and grades III–IV GVHD were 41% and 9%, respectively. All patients with GVHD responded fully to standard therapy (steroids ± tacrolimus) or therapy per BMT CTN0302, and all except 2 patients were rapidly weaned from all immunosuppressive agents. Of the thirty-six patients alive after day 100, only 1 of the 23 patients that received HLA-matched related, and 3 of 13 patients that received unrelated allografts, developed chronic GVHD. Twenty-six (56%) patients are alive, of whom 21 (45%) are in complete remission. There were no deaths secondary to infection or GVHD. CMV reactivation was detected in 11 of 36 (31%) patients, of whom 9 had GVHD. There was no CMV infection. Median (± SEM) CD4+ T cell counts were 99 ± 16/mL and 209 ± 49/mL on days 60 (n = 23) and 180 (n= 8), respectively. Corresponding values for CD8+ T cells were 248 ± 132/mL and 228 ± 161/mL on days 60 and 180, respectively. Patients with grade II–IV GVHD had significantly fewer peripheral blood (PB) CD4+Foxp3+ T cells compared to patients with grade 0–I GVHD (p<0.05). Development of grade II–IV GVHD negatively correlated with the expression of the Foxp3 (p<0.05) and was associated with relatively higher expression of interferon-γ mRNA (p=0.08) in PB, suggesting higher effector function in the absence of Tregs in patients with grade II–IV GVHD. No differences in IL-10 mRNA expression between patients with or without GVHD were found, while significantly higher expression of interleukin-2 mRNA was detected in patients with grade II–IV GVHD (p<0.025). These results indicate that high-dose post-transplantation Cy is effective as a single agent strategy for limiting acute and chronic GVHD after myeloablative HLA-matched related and unrelated allografting; this approach also limits the need for prolonged immunosuppression, resulting in favorable immunoreconstitution with few opportunistic infections in this unfavorable group of patients. Longer follow-up and larger numbers of patients are needed to assess the impact of this strategy on survival.

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A Multicenter Phase II Study Using a Dose Intensified Pediatric Regimen in Adults with Untreated Acute Lymphoblastic Leukemia.

Blood ◽

10.1182/blood.v108.11.1858.1858 ◽

2006 ◽

Vol 108 (11) ◽

pp. 1858-1858 ◽

Cited By ~ 3

Author(s):

Daniel J. DeAngelo ◽

Lewis B. Silverman ◽

Stephen Couban ◽

Suzanne Dahlberg ◽

Philip C. Amrein ◽

...

Keyword(s):

Phase Ii ◽

De Novo ◽

Lymphoblastic Leukemia ◽

Demographic Data ◽

Philadelphia Chromosome ◽

Remission Induction ◽

Intrathecal Therapy ◽

High Dose ◽

Childhood All

Abstract Background: In children with ALL, current chemotherapy regimens produce an event-free survival (EFS) of greater than 80%. Adults with ALL have a much poorer prognosis, with EFS rates of 30–40%. Recent retrospective studies suggest that young adult patients may have superior outcomes when treated on more intensive pediatric regimens, but prospective studies are lacking. A phase II trial was performed in an effort to determine if an intensive pediatric regimen can be administered to adults with ALL. Methods: The therapeutic backbone of this protocol is based upon the high-risk arm of the DFCI Childhood ALL Consortium Protocol 00–01. Patients with newly diagnosed ALL were enrolled and received intensive multiagent remission induction chemotherapy, which included doxorubicin, prednisone, vincristine, high-dose methotrexate, high-dose asparaginase, and triple intrathecal therapy. CNS prophylaxis included triple intrathecal therapy and cranial radiation. Intensification therapy consisted of 3 week courses of doxorubicin, vincristine, dexamethasone, 6-mercaptopurine and 30 weeks of high-dose asparaginase that was individually dosed in order to maintain asparagine depletion. Continuation therapy consisted of 3 week courses of vincristine, dexamethasone, methotrexate and 6-mercaptopurine for a total of 2 years from an established complete remission (CR). Results: 71 patients have been enrolled to date. Although there was no initial upper age restriction, the protocol was amended to include only patients between the ages of 18–50 with de novo ALL; this amendment excluded 4 patients from the analysis. Two patients were enrolled but never received therapy. Demographic data are available for 61 evaluable patients. The median age was 28 years, (range, 18–50), 65% were male, 75% had B-lineage phenotype, and 13% were Philadelphia chromosome positive. In the 54 patients for whom response data was available, the 4 week CR rate was 82%. Among the patients who had the opportunity to complete Intensification therapy, asparaginase data was available for 23 patients, 18 (78%) of whom completed all 30 weeks. One death occurred during induction therapy from sepsis. Four patients developed grade 3 pancreatitis and one patient died of grade 5 pancreatitis. The latter case represented the only remission death on study. There were two cases of osteonecrosis, 10 cases of thrombosis/embolism and 12 cases of neutropenic infection that occurred during the post-remission period. At the median follow-up time of 18.4 months, the estimated EFS is 75% (95%CI: 61–89%) and the overall survival is 79% (95%CI: 65–93%). Conclusions: These results suggest that administration of a dose intensified pediatric-like strategy is feasible. Although the high EFS rate requires longer follow up and larger confirmatory studies, such intensive treatment of young adults with ALL could represent a major therapeutic advance.

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A Multicenter Phase II Study Using a Dose Intensified Pediatric Regimen in Adults with Untreated Acute Lymphoblastic Leukemia.

Blood ◽

10.1182/blood.v110.11.587.587 ◽

2007 ◽

Vol 110 (11) ◽

pp. 587-587 ◽

Cited By ~ 16

Author(s):

Daniel J. DeAngelo ◽

Suzanne Dahlberg ◽

Lewis B. Silverman ◽

Stephen Couban ◽

Philip C. Amrein ◽

...

Keyword(s):

Young Adults ◽

Phase Ii ◽

De Novo ◽

Lymphoblastic Leukemia ◽

Philadelphia Chromosome ◽

Treatment Strategies ◽

Intrathecal Therapy ◽

High Dose ◽

Childhood All

Abstract Background: Current chemotherapy regimens in children with ALL produce event-free survival (EFS) rates of greater than 80%. In contrast, adults with ALL have a much poorer prognosis, with EFS rates of 30–40%. Recent retrospective studies suggest that young adults may have superior outcomes when treated with intensive pediatric regimens. Unfortunately, prospective studies are lacking. This phase II trial was performed to determine if an intensive pediatric regimen could be administered to adults with ALL. Methods: The therapeutic backbone of this protocol is based on the high-risk arm of the DFCI Childhood ALL Consortium Protocol 00-01. Patients with newly diagnosed ALL received induction chemotherapy, which included doxorubicin, prednisone, vincristine, high-dose methotrexate, L-asparaginase (L-asp), and triple intrathecal therapy. CNS prophylaxis included triple intrathecal therapy and cranial radiation. Intensification therapy consisted of ten 3-week courses of doxorubicin, vincristine, dexamethasone, 6-mercaptopurine and 30 weeks of L-asp that was dosed to maintain asparagine depletion, defined as an L-asp level between 0.1 and 0.14. Continuation therapy consisted of 3 week courses of vincristine, dexamethasone, methotrexate and 6-mercaptopurine for a total of 2 years from an established complete remission (CR). Results: 89 patients have been enrolled and treated to date. The first 75 eligible patients were used for this analysis, 73 of whom had on-study data. Although there was no initial upper age restriction, the protocol was amended to include only patients between the ages of 18–50 with de novo ALL, which excluded 4 patients from the analysis. The median age was 28 years, (range, 18–50), 60% were male, 74% had B-lineage phenotype, and 20% were Philadelphia chromosome positive. The CR rate after 4 weeks was 84%. 39 patients had the opportunity to complete L-asp intensification therapy, and 27 (69%) completed all 30 weeks. The median L-asp dose was 16,582 U/m2 (starting dose was 12,500 U/m2). One death occurred during induction therapy (sepsis). Nine patients developed pancreatitis, one of whom died. This last case represented the only remission death on study. Two patients developed osteonecrosis, 14 thrombosis/embolism and 23 neutropenic infection during the post-remission period. With a median follow-up time of 15.3 months, the estimated 2-yr EFS is 72.5% (95%CI: 61–84%) and the estimated 2-yr overall survival (OS) is 77.1% (95%CI: 67–95%). Conclusions: The administration of a dose intensified pediatric regimen to adults with ALL is feasible. Although the high EFS and OS rates require longer follow up, such intensive treatment strategies for young adults with ALL could represent a major therapeutic advance.

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Autologous Transplantation in De Novo Non-Promyelocytic Acute Myeloid Leukemia (AML) Patients in First Complete Remission (CR1) with Peripheral Blood Stem Cell (PBSC) Collection Following Consolidation with High-Dose Cytarabine and Etoposide: A Single Institution Experience

Blood ◽

10.1182/blood.v112.11.4461.4461 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4461-4461

Author(s):

Eugene Choi ◽

Lingyi Chen ◽

Srikanth Nagalla ◽

Vamshi Kaveti ◽

Regina Mullaney ◽

...

Keyword(s):

De Novo ◽

Disease Free Survival ◽

High Dose ◽

Free Survival ◽

Kaplan Meier ◽

Cd34 Cells ◽

High Dose Cytarabine ◽

Lost To Follow Up ◽

Disease Free

Abstract INTRODUCTION: Autologous PBSC transplant is an important yet evolving treatment modality for patients with AML. However, the ideal mobilization regimen from which to collect PBSC remains in question. Previous reports have indicated that highdose cytarabine with etoposide is both safe and effective in terms of successful PBSC procurement, subsequent engraftment, and disease outcome. METHODS: At our institution from 1994 to 2007, 38 consecutive patients with de novo non-promyelocytic AML in first complete remission following conventional induction chemotherapy were consolidated with high-dose cytarabine (2000mg/m2 IV q12h × 8 doses, days 1–4) and etoposide (40mg/kg IV over 96h) followed by G-CSF 5 mg/kg subcutaneously starting d14 until completion of PBSC collection. Patients underwent myeloablative therapy with busulfan (1mg/kg po q6h × 16 doses, days –7 to -4) and etoposide (60 mg/kg IV over 10h, day -3) with PBSC infusion occurring on day 0 with daily G-CSF 5 mg/kg. Data regarding stem cell yield, engraftment and patient outcome was collected retrospectively. RESULTS: The average patient age was 44 years (range 19–70). Following consolidation, at least 2×106 CD34 cells/kg were isolated from all 38 patients with a median of 9.4×106 (range 2.2–43) CD34 cells/kg over a mean of 4 collections (range 1–11). Overall, 36 of 38 (95%) remained in CR and went onto PBSC transplant (one died from infectious complications during consolidation, one relapsed before transplant). The median number of stem cells infused was 8.8×106 CD 34 cells/kg (range 2.2–47). All 36 patients engrafted with the mean number of days to neutrophil recovery (ANC>500) being 11 (range 8–17) and the mean number of days to platelet recovery (>20,000) being 12 (range 8–19). Disease-free outcomes in patients undergoing PBSC transplant while in CR1 are presented in Figure 1. The 3y overall survival in all pts was 66%, and 56% at 5y. For good-risk cytogenetic patients, 3y OS was 78% and the 5y OS was 75%. For intermediate-risk cytogenetic patients, OS was 47% and 36% at 3y and 5y respectively. Three patients with poor cytogenetics were autulogously transplanted. One patient relapsed at day 111 and expired at day 450. The second patient remains in CR at day 246. The third patient relapsed at day 104 and expired at day 322. CONCLUSION: In patients with de novo non-promyelocytic AML in CR1, consolidation with high-dose cytarabine plus etoposide is safe and provides excellent yield of PBSCs upon growth factor accelerated hematological recovery. Subsequent engraftment after autologous transplanation is rapid. Our outcomes support the viability of this regimen in patients with good and intermediate-risk cytogenetics. Figure 1: Kaplan-Meier analysis of disease-free survival following autologous PBSC transplant. Cytogenetic analysis was unavailable in 5 patients, and 1 patient was lost to follow-up. Figure 1:. Kaplan-Meier analysis of disease-free survival following autologous PBSC transplant. Cytogenetic analysis was unavailable in 5 patients, and 1 patient was lost to follow-up.

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Concomitant Thrombotic Microangiopathy and Rejection in a Recent Kidney Transplant: A Case Study

10.31487/j.tcr.2020.01.01 ◽

2020 ◽

pp. 1-4

Author(s):

Muhammad A. Bukhari ◽

Abdulaziz Al-Thumali ◽

El-Sadig Yousif ◽

Muhammad A. Bukhari ◽

Najla K Almalki ◽

...

Keyword(s):

Kidney Transplant ◽

Thrombotic Microangiopathy ◽

De Novo ◽

Kidney Transplant Recipient ◽

Calcineurin Inhibitors ◽

Armed Forces ◽

Post Transplantation ◽

Medical Interventions ◽

Antibody Mediated Rejection ◽

Life Threatening

Thrombotic microangiopathy (TMA) is an uncommon, life-threatening complication that adversely affects kidney transplant recipient and allograft survival. Post-transplantation TMA can occur as recurrence of the primary TMA or as a de novo condition. The latter can be triggered by numerous factors post-transplantation including calcineurin inhibitors, certain infections and antibody-mediated rejection. Rejection-associated TMAs carry a significantly lower graft survival rate compared with post-transplant TMAs that are not associated with rejection. In this case report, we present a rare case of rejection-associated TMA in a recently transplanted renal allograft that was managed in Al-Hada Armed Forces Hospital. Despite the poor expected outcome of this condition; the patient was successfully treated after early initiation of medical interventions. Transplantation teams may face many challenges managing such a combination of medical conditions, which may halt pursuing appropriate diagnostic and therapeutic measures in a timely fashion. This article highlights some of these challenges for better understanding of such a complex condition.

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Myeloablative Conditioning of Patients with Myelofibrosis with Myeloid Metaplasia Using i.v. Treosulfan and Autologous Peripheral Blood Progenitor Cell Transplantation (PBPCT) with High Doses of CD34+ Cells Results in Hematologic Responses - 32 Months Follow-Up of Three Patients and Short-Term Results of a New Study.

Blood ◽

10.1182/blood.v106.11.5515.5515 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5515-5515

Author(s):

Stefan Fruehauf ◽

Eike C. Buss ◽

Julian Toplay ◽

Hans H. Kreipe ◽

Anthony D. Ho

Keyword(s):

Multicenter Study ◽

Autologous Transplantation ◽

Conditioning Regimen ◽

Allogeneic Transplantation ◽

High Dose ◽

Post Transplantation ◽

Myeloid Metaplasia ◽

Cd34 Cells ◽

Myelofibrosis With Myeloid Metaplasia

Abstract Myelofibrosis with myeloid metaplasia (MMM) is a chronic myeloproliferative disorder. Myeloablation with high-dose treosulfan and autologous PBPCT provides a palliative approach. A minimum of 5 x 106 CD34+ cells/kg was collected in all patients after G-CSF-priming (16 μg/kg/d for 4 days). Myeloablation consisted of treosulfan (total dose 42 g/m2). To date we have transplanted 3 patients, all female on an individual basis. We observed a prolonged time to reconstitution of leucocytes > 1/nl post transplantation of 28 days (#1, #2) and 38 days (#3). The observation period post transplantation is 32 months now. Patient #1, who required erythrocyte transfusions twice weekly pretransplant received her last erythrocyte transfusion on day 56; her last Hb-value is 9.5 g/dl. The second patient (#2) recovered to platelet counts higher than pre transplantation (58/nl) at 3 months (143/nl) and had 125/nl at last follow-up. Pat. #3 showed a marked reduction of max. spleen size and a rise in Hb from 9 g/dl to 12 g/dl after 12 months, the last Hb value at 26 months was 7.6 g/dl and she received about 3 erythrocyte transfusions per month again. She then underwent allogeneic transplantation from her sister and is currently alive and well. Three male patients were treated in a new one-armed, multicenter study applying the aforementioned protocol. In two patients we observed again a prolonged reconstitution period of 28 (S1) and 44 (S2) days. In one patient (S1) leukocytosis and thrombocytosis resolved while transfusion dependent anemia persisted. In the second patient (S2) transfusion dependent anemia persisted. He received a backup transplantation but still remains transfusion-dependent. Patient S3 had a critical thrombocytopenia of 16/nl before transplantation and proved to be refractory to thrombocyte transfusions post-transplantation. He developed cerebral hemorrhage and died. The conditioning regimen was well tolerated and despite the prolonged aplasia period neutropenic fever was rare (median 1 day, range 0–6 days). The overall response rate was 60%, the mortality rate was 17% which is both compatible with previous data of autologous transplantation in MMM patients undergoing busulfan conditioning. This multicenter study is continuing to recruit patients (http://leukaemie.krebsinfo.de/kn_home/Studien/studie_101.html).

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