Allogeneic Hematopoietic Stem Cell Transplantation for Myeloma: Does the Melphalan Dose Matter?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3035-3035
Author(s):  
Jayesh Mehta ◽  
Sandeep Chunduri ◽  
Lisa Dobogai ◽  
Seema Singhal ◽  
Damiano Rondelli
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Bone Marrow Transplantation ◽  
Hematopoietic Stem Cell Transplantation ◽  
Performance Status ◽  
Hematologic Malignancies ◽  
Refractory Disease ◽  
Donor Age ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract The dose of melphalan affects the outcome of autotransplantation in myeloma significantly. Regimens not containing melphalan or doses of melphalan lower than 200 mg/m2 have been shown to result in inferior disease-free (DFS) and overall (OS) survival (Mehta J, Singhal S. High-dose chemotherapy and autologous hematopoietic stem cell transplantation in myeloma patients under the age of 65 years. Bone Marrow Transplantation advance online publication, 6 August 2007; doi:10.1038/sj.bmt.1705799). However, whether the melphalan dose affects the outcome of allogeneic HSCT is unknown. The outcome of 30 patients undergoing submyeloablative allogeneic HSCT after 100 mg/m2 (n=24) or 140 mg/m2 (n=6) melphalan was studied to determine the effect of melphalan dose-intensity. The higher melphalan dose was combined with 150 mg/m2 fludarabine. As the figures below show, DFS and OS appeared to be better after the higher dose of melphalan on unadjusted analysis. Figure Figure The following variables were studied for their effect on OS: patient age, donor age, chemorefractoriness, HLA mismatch, melphalan dose, performance status, and LDH level. The factors found to be significant in univariate analysis - donor age, performance status, LDH, and chemorefractoriness - were entered into a Cox model. The dose of melphalan was forced into the final model. The table below shows the factors found to significantly affect relapse, DFS and OS in multivariate analysis. No factor was found to affect transplant-related mortality significantly. Adverse variable RR P Relapse Refractory disease 5.5 0.02 DFS Elevated LDH 3.5 0.017 Donor age >45 3.4 0.024 Refractory disease 3.5 0.044 OS Elevated LDH 8.0 0.002 Performance status 2/3 5.8 0.003 Donor age >45 4.1 0.031 The melphalan dose did not affect relapse (P=0.37), DFS (P=0.16) or OS (P=0.12) significantly. These data suggest that 100 mg/m2 and 140 mg/m2 melphalan doses appear to result in comparable outcomes after allogeneic HSCT in myeloma. This is probably because the immunologic graft-versus-myeloma effect compensates for the reduced anti-myeloma efficacy of the lower melphalan dose. Whether higher melphalan doses, used successfully as pre-allograft conditioning for hematologic malignancies (Singhal S, Powles R, Treleaven J, Horton C, Mehta J. Melphalan alone prior to allogeneic bone marrow transplantation from HLA-identical sibling donors for hematologic malignancies: alloengraftment with potential preservation of fertility. Bone Marrow Transplant1996; 18:1049–1055), confer any benefit for myeloma allografts remains to be seen.

scholarly journals Detection of Cells with Low Side Scatter and Dimmer CD45 Expression after Allogeneic Hematopoietic Stem Cell Transplantation Predicts Good Survival

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3207-3207
Author(s):  
Yoshimitsu Shimomura ◽  
Hayato Maruoka ◽  
Yotaro Ochi ◽  
Yusuke Koba ◽  
Yuichiro Ono ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Bone Marrow Transplantation ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Marrow Transplantation ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract <Introduction> Hematogones are lymphoblast-like cells that increase transiently in the bone marrow and have a characteristic profile of normal B cell precursors co-expressing CD10 and CD19. A cluster of hematogones is often found in the region of low side scatter and dimmer CD45 expression (SSC low CD45 dim), which also includes lymphoid and myeloid precursors, basophils, and partial components of natural killer cells. However, in steady state healthy adult bone marrow, SSC low CD45 dim populations are hardly detectable. In the bone marrow of patients recovering from chemotherapy or bone marrow transplantation, SSC low CD45 dim populations occasionally appear, with the majority of the population consisting of hematogones, especially in patients in complete remission (CR). Studies have shown that increased hematogones in patients with high-risk hematological malignancies after allogeneic hematopoietic stem cell transplantation (HSCT) improved survival. The specific detection of hematogones is difficult because multicolor flow cytometry is necessary to exclude myeloid/lymphoid blasts in active leukemia patients. However, after allogeneic HSCT in patients with leukemia and confirmed CR or malignant lymphoma without bone marrow invasion, hematogones can be easily detected as cells with SSC low CD45 dim populations. <Patients and methods> This retrospective case analysis included 88 patients treated with allogeneic HSCT at our hospitals from October 2010 to November 2014. The cases included acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) in CR at the time of allogeneic HSCT, chemo-naïve or azacitidine-treated myelodysplastic syndrome (MDS) and malignant lymphoma (ML) or adult T cell leukemia/lymphoma (ATL) with marrow CR or without bone marrow invasion. We excluded 8 patients without engraftment. The remaining 80 patients underwent bone marrow aspiration around 28 days after HSCT and were confirmed to be in CR. Bone marrow cells were stained with APC-Cy7-conjugated CD45 and analyzed using FACSCanto. Patients were defined as being simply detected hematogones (SHG)-positive if 0.6%, which is the median proportion of SSC low CD45 dim cells in this study, or more of total nuclear cells were SSC low CD45 dim; the others were defined as SHG-negative. <Results> The median follow-up of survivors of our cohort was 773 (81-1593) days. Primary diagnoses were AML (n=36), ALL (n=21), MDS (n=8), and ML or ATL (n=15). They were treated with bone marrow transplantation (n=51), peripheral blood stem cell transplantation (n=6), and cord blood transplantation (n=23). Among them, 40 were SHG-positive and 40 were SHG-negative. Overall survivals (OS) at 2 years was 94.8% and 58.2% (p<0.001), event free survival (EFS) at 2 years was 94.9% and 46.5% (p<0.001). Cumulative incidence of relapse at 2 years was 5.1% and 34.0% (p<0.001), and cumulative incidence of treatment related mortality (TRM) at 2 years was 0% and 20.6% (p=0.0059) in SHG-positive and SHG-negative groups, respectively. Cumulative incidence of acute graft-versus-host disease (aGVHD) at day 100 was 68.3% and 65.5% (p=0.31) and for severe aGVHD (grade II-IV) was 31.8% and 36.3% (p=0.87) in SHG-positive and SHG-negative groups, respectively. Age ≥50 years, sex, hematopoietic cell transplant-comorbidity index over 2, disease risk index (DRI), myeloablative conditioning regimen and donor source were entered into multivariate analysis, which identified SHG-positive and a low or intermediate DRI as independently associated with a good prognosis. <Conclusion> Thus, the presence of SHG at day 28 predicts improved OS and EFS, and a lower incidence of relapse and TRM. This population of cells is easily detectable, providing useful information for outcome predictions. Patients without SSC low CD45 dim populations should be carefully observed after allogeneic HSCT. Disclosures No relevant conflicts of interest to declare.

scholarly journals Haploidentical, unmanipulated, G-CSF–primed bone marrow transplantation for patients with high-risk hematologic malignancies

Blood ◽  
2013 ◽  
Vol 121 (5) ◽  
pp. 849-857 ◽  
Author(s):  
Paolo Di Bartolomeo ◽  
Stella Santarone ◽  
Gottardo De Angelis ◽  
Alessandra Picardi ◽  
Laura Cudillo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Bone Marrow Transplantation ◽  
High Risk ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Marrow Transplantation ◽  
Hematologic Malignancies ◽  
Hematopoietic Stem ◽  
Key Points

Key Points Haploidentical, unmanipulated, G-CSF–primed bone marrow transplantation. Haploidentical hematopoietic stem cell transplantation for hematologic malignancies.

The Impact of Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescents with Recurring Hodgkin’s Lymphoma: An EBMT Study on 151 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3061-3061 ◽  
Author(s):  
Alexander Claviez ◽  
Carmen Canals ◽  
Marc Boogaerts ◽  
Jerry Stein ◽  
Stephen Mackinnon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Performance Status ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
The Impact ◽  
Time Point

Abstract Background: Allogeneic hematopoietic stem cell transplantation (HSCT) has become a therapeutic option for patients with recurring Hodgkin’s lymphoma (HL). Standardized inclusion criteria, the optimal time point and the type of conditioning regimen have, however, not been clarified yet. Moreover, high treatment related mortality (TRM) has hampered the widespread use of this procedure. Only few data are available on the impact of allogeneic HSCT in pediatric and adolescent patients. Patients and Methods: We analyzed patients registered in the EBMT Lymphoma Database (age < 21 years at transplantation) who received an allogeneic HSCT for relapsed or refractory HL between 1987 and 2005. Results: A total of 151 patients (56% male) were included. Median age at diagnosis and HSCT was 15 and 18 years, respectively. 57% of patients had received three or more lines of treatment prior to allogeneic HSCT including autologous HSCT in 77 patients with a median interval of 18 months between autologous and allogeneic HSCT. The majority of donors were matched related (63%), followed by matched unrelated (25%) and mismatched donors. A full myeloablative conditioning regimen was given to 40% of patients and 60% received a regimen of reduced intensity. Disease status at HSCT was sensitive (complete or partial remission) in 59% and refractory (no change or progression) in 41%. 23% of the patients developed grade 2–4 acute graft versus host disease (GvHD). Of 35 patients with evaluable chronic GvHD, limited and extensive GvHD were balanced. With a median follow-up of 25 months (maximum 154), 75 patients (50%) are alive and 59 of them disease-free. 56 patients (37%) relapsed after a median time of 5 months (<1 to 36 months) and only 16 were alive at last contact. The probability for progression-free survival (PFS) at 2 and 5 years were 39% and 29% respectively. The cumulative incidences (CI) for relapse at 1, 2 and 5 years were 29%, 37% and 44%, respectively, whereas the CI for TRM at 1, 2 and 5 years were 20%, 24% and 27%, respectively. In multivariate analysis, HLA disparity (p=.002), HSCT before 2001 (p=.01) and female sex (p=.02) were associated with a higher TRM, while poor performance status (p=.005) and refractory disease (p=.04) resulted in an inferior PFS. Reduced treatment intensity had no impact on relapse rate within one year after HSCT but was associated with a higher incidence of relapse (p=.02) beyond 12 months. The PFS and TRM of patients without adverse prognostic factors (HSCT >2001, matched donors and good performance status at HSCT) at 1, 2 and 5 years was 67%, 50% and 43%, and 11%, 17% and 17%, respectively. Conclusion: This study of young patients with HL receiving allogeneic HSCT indicates a comparable outcome to adult patients. Transplantation was beneficial especially for patients with a good performance status, HSCT in recent years and available matched donors. Allogeneic HSCT should be carefully selected at an early time point in children failing standardized primary and salvage treatment.

Human Herpes Virus-6 and Clinical Manifestations After Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1960-1960
Author(s):  
Raffaella Greco ◽  
Francesca Lorentino ◽  
Daniela Clerici ◽  
Francesca Matteazzi ◽  
Alessandra Forcina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cerebrospinal Fluid ◽  
Stem Cell ◽  
Viral Load ◽  
Hematopoietic Stem Cell Transplantation ◽  
Clinical Manifestations ◽  
Median Viral Load ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Clinical Complications

Abstract Abstract 1960 BACKGROUND: Human herpesvirus 6 (HHV-6) is increasingly recognized as an opportunistic and potentially life-threatening pathogen in recipients of allogeneic Hematopoietic Stem Cell Transplantation (HSCT). Reported clinical manifestations of HHV-6 infection in transplanted patients are skin rash, interstitial pneumonia, bone marrow suppression and encephalitis. Moreover, an increasing number of clinical reports suggest that HHV-6 can facilitate the occurrence of other severe clinical complications of allogeneic HSCT, including Graft-versus-Host Disease (GvHD), ultimately increasining transplant-related mortality. Still, the actual incidence of HHV-6 infection in recipients of HSCT and the causative link between infection and clinical complications remain elusive, mostly due to the small and heterogeneous patient cohorts analyzed to date. METHODS: From January 2009 to July 2011, we retrospectively evaluated 43 consecutive adult patients (median age 51 years) who developed positivity to HHV-6 after allogeneic HSCT for high-risk hematological malignancies. Stem cell donor was for 30 patients family haploidentical, for 5 an HLA identical sibling, and for 8 an unrelated volunteer (1 of which cord blood). The viral load was determined by quantitative PCR in cell-free body fluids such as plasma, bronchoalveolar lavage, cerebrospinal fluid, bone marrow aspirates or in gastrointestinal biopsies. At the time of positivity all patients were receiving acyclovir as viral prophylaxis except 5. Sixteen patients had clinical acute GvHD at time of HHV-6 positivity (grade III-IV in 14), and 33 were profoundly immunosuppressed with variable association of 2–4 immunosuppressive drugs (steroids included). Moreover concomitant CMV positivity was detected in 11 patients, while a severe neutropenia in 12. RESULTS: Median time from allogeneic HSCT to HHV-6 reactivation was 36 days (range: 7–625). In 19 patients HHV-6 was detected in plasma, with a median viral load of 19,454 cp/mL (34-4,524,600); 15 had concomitant fever, 5 skin rash of new onset, 4 impaired liver function, and 5 developed cytopenia subsequently to the infection. In 7 patients HHV-6 was detected in the bone marrow: the median viral load was 163'800 cp/mL (568-1'552'982). In 8 patients, all febrile, HHV-6 was observed in bronchoalveolar lavage samples with a median of 4'149 cp/mL (85–39250). In 16 patients, 10 with documented gut aGvHD, 11 with diarrhoea, HHV-6 was detected in gastrointestinal biopsies with a median of 7'510 cp/mL (120-4'524'600). HHV-6 was found in cerebrospinal fluid in 4 cases (all within 30 days after HSCT); the median viral load was 29'352 cp/mL (4'508-1'552'982); all these patients experienced encephalitis with confusion and anxiety, 2 suffered seizures and 3 showed abnormal findings on brain MRI. Amongst patients with organ localizations of HHV-6 only 28% had concomitant plasma positivity. HHV-6 positivity led to antiviral pharmacological treatment only when associated with clinical manifestations (n=21), using as first choice therapy foscarnet. Amongst the total 43 patients with documented HHV-6 positivity 11 completely solved the clinical event, whereas 19 (44%) died. CONCLUSIONS: HHV-6 infection/reactivation is associated with high morbidity and mortality in patients who undergo allogeneic HSCT. HHV-6 infection typically occurred close to the time of neutrophil engraftment. HSCT from an HLA-mismatched donor and steroid administration were associated with increased risk of active HHV-6 infection. Development of encephalitis was associated with high HHV-6 viral load. The regular monitoring of HHV-6 DNA in allogeneic HSCT recipients, using a real-time PCR assay, may be useful for identifying active HHV-6 infection and for the introduction of a pre-emptive treatment, possibly reducing the incidence of the most severe clinical complications. Disclosures: No relevant conflicts of interest to declare.

Inherited Predisposition to Myelodysplastic Syndrome and Acute Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. SCI-31-SCI-31
Author(s):  
Jane E. Churpek
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Genetic Testing ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Clinical Care ◽  
Hematologic Malignancies ◽  
Ongoing Research ◽  
Hematopoietic Stem

Although generally thought of as pediatric conditions, inherited forms of myelodysplastic syndrome (MDS) and acute leukemia (AL) are increasingly recognized among adult patients. At present, at least nine genes, including ANKRD26, CEBPA, GATA2, PAX5, RUNX1, SRP72, TERC, TERT, and TP53, are known to cause familial MDS and/or AL syndromes. Several other promising candidate genes are emerging from ongoing research on the many pedigrees identified without a mutation in one of these already recognized genes. Clinical recognition of individuals with these syndromes is essential for optimal care of the patient and his/her at-risk family members and requires familiarity with the subtle clinical features of each syndrome and a high index of suspicion by the treating physician. Once recognized, genetic testing should be performed to identify the specific syndrome present as each can have unique aspects to their clinical care. For example, individuals with familial MDS/AL due to TERT or TERC abnormalities require monitoring of lung function and screening for head and neck and anogenital cancers, whereas individuals with platelet dysfunction due to familial platelet disorder/RUNX1 or ANKRD26 mutations require careful planning prior to surgical procedures to prevent bleeding complications. Due to significant overlap in the clinical presentation, often a multigene-based approach to genetic testing is necessary. Unique aspects of genetic testing in this population include: 1) tissue type selection as many of the genes that cause the familial MDS/AL syndromes are also somatically mutated in hematologic malignancies so results from DNA derived from peripheral blood or bone marrow in an individual with MDS or AL are difficult to interpret; and 2) urgency as allogeneic hematopoietic stem cell transplantation may be pursued quickly and requires knowledge of the specific mutation in the family to identify the optimal stem cell donor. The management of affected individuals who have not yet developed hematologic malignancies can be challenging as many may show morphologic signs of dysplasia in the bone marrow that may not truly represent overt malignancy. The decision of when to pursue allogeneic hematopoietic stem cell transplantation with curative intent is especially difficult. Ongoing research to define the specific events that trigger malignant transformation and how to optimally detect these events is underway. Practical algorithms for the clinical recognition, genetic testing, and management of individuals with these syndromes based on currently available knowledge as well as research seeking to improve the clinical care of these patients will be explored. A summary of the yield of next generation sequencing-based genetic testing strategies for familial presentations of MDS/AL will also be provided. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document